7. COPD Flashcards
what is COPD?
disease with progressive airflow limitation that is not fully reversible. associated with abnormal inflammatory response of lungs to toxins (can be smoking)
two types of COPD?
chronic bronchitis, emphysema
defn of chronic bronchitis?
productive cough on most days for a minimum of 3 mo/year for at least 2 yrs. clinical dx
def of emphysema?
enlargement of airspaces distal to the terminal bronchiole, destruction of the alveolar walls. no fibrosis. pathological dx.
risk factors for COPD?
cig smoke
occupational dust and particles
environmental tobacco smoke
air pollution
how does exposure to inhaled toxins yield the COPD disease state?
inflammatory process in response to the inhaled toxins, neutrophils release proteases, leads to inflammation and loss of elastic recoil
the two main problems in COPD?
- small airway disease (airway inflammation/remodeling)
2. parenchymal destruction (loss of elastic recoil)
what does the ‘obstructive’ element of COPD refer to?
airway narrowing and airflow obstruction
if smoke primarily affects small airways, then the phenotype will be?
chronic bronchitis – mucosal inflammation, fibrosis
if smoke primarily affects parenchyma and alveoli, then the phenotype will be?
emphysema – disrupted alveolar attachments, loss of elastic recoil
phenotype of chronic bronchitis?
productive cough, hypoxia/cyanosis, pulmonary HTN
phenotype of emphysema?
breathlessness, cachexia (wasting)
what is alpha-1-anti-trypsin?
protein made in liver, inhibitor of circulating proteases in the lungs. (ie, inhibits proteases from damaging lung)
what will happen if someone has an alpha-1-anti-trypsin deficiency? (recessive trait)
w this deficiency + cig smoking, will dev COPD earlier on than would with just cigs.
if someone has an alpha-1-anti-trypsin deficiency but does not smoke cigs, will they dev COPD?
improbable
using spirometry, how would you dx obstructive disease?
based on FEV1/FVC radio. usually lower than 70% of normal.
if FEV1/FVC ratio is low, what are the 3 possible diagnoses?
- chronic bronchitis
- emphysema
- CF
what happens with FRC in emphysema?
incr due to reduced elastic recoil of the lung. hypervolume
what happens with FRC in chronic bronchitis?
FRC is normal, elastic recoil is not affected.
what happens with RV in emphysema?
RV is increased due to air trapping. pt is unable to exhale all the air completely.
what happens with RV in chronic bronchitis?
RV is increased due to air trapping. pt is unable to exhale all the air completely.
what happens with FVC in emphysema?
may be normal or decr, due to air trapping.
what is FVC/VC?
total amt of air that can be exhaled after a deep inhalation. dependent on RV.
what happens with FVC in chronic bronchitis?
may be normal or decr, due to air trapping.
what is FRC?
balance between the outward expansion of the chest wall and the inward/elastic recoil of the lung
what is RV?
amt of air in the lungs at the end of forced vital capacity
what is TLC?
amt of air in the lungs after a deep inhalation. detd by the elastic recoil of the lungs and insp muscle strength.
what happens with TLC in emphysema?
inc due to reduced elastic recoil of the lung
what happens with TLC in chronic bronchitis?
normal because elastic recoil is not affected.
what happens with DLCO in emphysema?
decr due to destruction of the alveolar-cap membranes as a result of proteases
what happens with DLCO in chron bron?
DLCO is normal (disease is in airways, not gas exchange units)
the list of possible treatments for COPD?
- smoking cessation
- pharm treatments (bronchodilators, glucocorticosteroids, A1AT therapy)
- 02
- pulmonary rehab
- surgery
have any drugs been shown to modify the long term decline in lung function?
no
what do bronchodilators do?
inc cAMP which relaxes bronchial smooth muscle.
what is the deal with glucocorticosteroids?
anti-inflammatory. ok using inhaled. not good for long term oral therapy because side effects outweigh benefits.
what does pulmonary rehab consist of?
exercise training - most pts with COPD have reduced the physical activities to reduce dyspnea. lungs have become deconditioned.
what might exacerbate COPD?
- environmental toxins
- bacterial infection
- viral infection
how is obstructive airway disease defined?
anything that causes an obstruction of flow of air
what is the first airway structure without cartilage and sub-mucosal glands? what about muscle in this area?
bronchioles. first airway with circumferential smooth muscle (spiral)
what are some features of bronchitis that we might see on slides?
- hypersecretion of mucus in airways, goblet cell hyperplasia.
- clustered inflammatory cells, alveolar macrophages
what is a bronchospasm in the setting of COPD
spasm of the smooth muscle-surrounded airways. referred to as an asthmatic component to COPD.
what can repair of damaged lung look like?
either re-epithelialization and restoration, or fibrous remodeling and scarring. re-epithelialization can either be native epithelium or metaplastic.
what does resp mucosa generally look like
ciliated, pseudostratified with scattered goblet cells
what will happen with continuous irritation and inflammation?
epithelium undergoes metaplasia. final mucosa may become squamous type. precursor to certain lung cancers
what are the three patterns of emphysema (at the alveolar level)?
- centriacinar
- panacinar
- distal acinar (aka paraceptal)
describe centriacinar emphysema?
destruction limited to resp bronchioles and central portions of acinus. most severe in upper lobes, assocd with cig smoking. smoking will damage most proximal tissue first.
describe panacinar emphysema?
involves entire alveolus distal to the term bronchiole. most severe in lower long, generally develops in pts with A1AT deficiency
describe distal acinar emphysema?
least common, localizes to fibrous septa or pleurae, leads to bullae formation.
in emphysema, what is it that actually destroys the tissue?
neutrophil elastase.
macrophage elastase
oxidants/reactive 02 species
neutrophil elastase does what?
destroys elastin and thus decr elastic recoil. also attacks connective tissue matrix thus degrading the supporting structures of the lung
what do oxidants/ROS do?
deplete anti-oxidants, incite tissue damage
definition of asthma?
hyper-responsiveness of tracheobronchial tree, leads to repeated episodes of bronchoconstriction and inflammation.
what is atopy?
genetic predisposition to type 1 hypersensitivity reaction
in asthma, what do the T2 helper cells do?
induce bronchial allergic inf response: interleukin secretion and stimulation of B lymphocytes to produce IgE (mast cell, vasodilation, edema)
what is the problem with the T2 helper response in asthma?
normally T1 and T2 cells maintain balance in our airways. in asthma, there is an imbalance with greater T2 response.
what happens when IgE (from T2 activity) triggers mast cell activation?
vasodilation, edema. Eosinophils may be recruited which secrete major basic protein which is damaging to epithelium, and causes further constriction.
what changes to the airway occur w asthma?
fibrosis of submucosa, thickened bronchial smooth muscle which may lead to spasms, thickened mucus secretions
bronchiectasis: definition
abnormal permanent dilatation of airways that affects airflow. usually secondary to chronic infection.
is bronchiectasis reversible
nope.
The types of cells in alveoli: what do they do?
Epithelial cell. comma shaped, flat.
P1 = type I pneumocyte. fragile, is site of gas exchange. cytoplasm is like arms extending out. can be confused with E.
P2 = Type II pneumocyte. has regenerative properties. makes surfactant.
M = macrophage. cleanup.
with irritated epithelium, what happens to the relative amts of goblet cells and cilia?
in bronchi: make more goblet cells, more mucus. fewer ciliated cells. basically trade pseudostratified tissue for mucus tissue.
what is the Reid index?
measure of the relative thickness of submucosal tissue to full epithelial surround. if less than 0.4, ok. if greater, consistent with chronic bronchitis
what is the difference between normal mucosa and squamous metaplasia?
normal: pseudostratified ciliated. every cell hits basement membrane.
squamous met: truly stratified. less ciliated.
which type of emphysema pattern is associated with spontaneous pneumothorax?
paraseptal (distal acinar)/bullus.
in A1AT deficiency, what emphysema pattern will you see?
panacinar, because deficiency is everywhere. may also see further damage in bases of lungs because neutrophils tend to congregate there (slightly more bloodflow/perfusion there)
what are the 2 types of asthma?
intrinsic, extrinsic
intrinsic asthma means what?
non-allergic. due to cold, exercise, resp tract infections
extrinsic asthma means what?
allergic. initiated by a type 1 hypersensitivity reaction.
asthma: histology?
- incr submucosal mucus glands
- hypertrophied smooth muscle
- inflammatory infiltrate with eosinophils
- thick mucus plug
what will you find in the mucus of an asthmatic?
- Charcot Leyden crystals (degranulated eosinophil membranes
- Curschmann spirals – whorls of shed epithelium
what characterizes bronchiactesis?
permanent airway dilatation. like an old rubber band that will not spring back. brittle.
