WEEK 1: Images of disease Airflow limitation and bronchial asthma) Flashcards
What is airflow Limitation?
What is the other name for airflow limitation?
Outline examples of major diffuse obstructive disorders
There is an increased in resistance to air flow caused by partial or complete obstruction at any level of the airways.
It is also called obstructive airway disease.
The major diffuse obstructive disorders are emphysema, chronic bronchitis, bronchiectasis, and asthma.
Describe the spirometry volumes for airflow limitation.
expiratory flow rate, usually measured as the forced expiratory volume at 1 second (FEV1), is significantly decreased.
forced vital capacity (FVC) is either normal or slightly decreased.
Describe emphysema.
Emphysema is characterized by permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls without significant fibrosis.
Emphysema is classified according to its anatomic
distribution.
Outline four major types of emphysema.
There are four major types of emphysema:
(1) Centriacinar/ Centrilobular:
*Affects the respiratory bronchioles.
*It is commonly associated with cigarette smoking and tends to affect the upper lobes of the lungs more prominently.
(2) Panacinar:
*Affects the alveolar ducts and alveolus.
*It is most strongly associated with alpha-1 antitrypsin deficiency, a genetic disorder that predisposes individuals to early-onset emphysema, particularly in the lower lung fields.
*Panacinar emphysema often affects the lower lung zones bilaterally.
(3) Distal acinar
*It is often seen in conjunction with chronic bronchitis and is associated with chronic exposure to irritants such as cigarette smoke and air pollution.
*Distal acinar emphysema can lead to significant destruction of lung tissue and impaired gas exchange.
(4) irregular.
*It may involve irregular areas of emphysematous destruction throughout the lung parenchyma.
*This type of emphysema can result from a variety of factors, including occupational exposures, inflammatory lung diseases, or a combination of factors.
Only the first two types cause significant airway obstruction, with centriacinar emphysema being about 20 times more common than panacinar disease.
Discuss Chronic bronchitis.
Chronic bronchitis is diagnosed on clinical grounds:
it is defined by the presence of a persistent productive cough for at least 3
consecutive months in at least 2 consecutive years.
It is common among cigarette smokers and urban dwellers in smog-ridden cities.
Early phase is characterized by cough with mucoid sputum, but airflow is not obstructed.
Some patients with chronic bronchitis have evidence of hyperresponsive airways, with
intermittent bronchospasm and wheezing (asthmatic bronchitis),
while other bronchitis patients, especially heavy smokers, develop chronic outflow obstruction, usually with associated emphysema (COPD).
Describe the pathogenesis of Chronic bronchitis.
The distinctive feature of chronic bronchitis is hypersecretion of mucus, beginning in the large airways.
most important cause is cigarette smoking, other air pollutants, such as sulfur dioxide and nitrogen dioxide, may contribute.
These environmental irritants induce hypertrophy of mucous glands in the trachea and bronchi as well as an increase in mucin-secreting goblet cells in the epithelial surfaces of smaller bronchi and bronchioles.
These irritants also cause inflammation marked by the infiltration of macrophages, neutrophils, and lymphocytes.
It is postulated that many of the effects of environmental irritants on respiratory epithelium are mediated by local release of cytokines such as IL-13 from T cells and innate lymphoid cells.
The transcription of the mucin gene in bronchial epithelium and the production of neutrophil elastase are increased as a consequence of exposure to tobacco smoke.
Microbial infection often is present but has a secondary role, chiefly by maintaining inflammation and exacerbating symptoms.
Describe the morphology of Chronic bronchitis.
the mucosal lining of the larger airways usually is hyperemic and swollen by edema fluid and is covered by a layer of mucinous or mucopurulent secretions.
The smaller bronchi and bronchioles also may be filled with secretions.
The diagnostic feature of chronic bronchitis in the trachea and larger bronchi is enlargement of the mucus secreting glands.
(Fig. 13.9).
The magnitude of the increase in size is assessed by the ratio of the thickness of the submucosal gland layer to that of the bronchial wall (the Reid index—normally 0.4).
Variable numbers of inflammatory cells, largely lymphocytes and macrophages but sometimes also admixed neutrophils, are frequently seen in the bronchial mucosa.
Chronic bronchiolitis (small airway disease), characterized by goblet cell metaplasia, mucous plugging, inflammation, and fibrosis, also is seen.
In severe cases, there may be complete obliteration of the lumen as a consequence of fibrosis (bronchiolitis obliterans).
It is the submucosal fibrosis that leads to luminal narrowing and airway obstruction. Emphysematous changes often coexist.
Outline clinical features of Chronic bronchitis.
Clinical Features
The course of chronic bronchitis is quite variable.
In some patients, cough and sputum production persist indefinitely without ventilatory dysfunction, while others develop COPD with significant outflow obstruction marked by hypercapnia, hypoxemia, and cyanosis.
Patients with chronic bronchitis and COPD have frequent exacerbations, more rapid disease progression, and poorer outcomes than those with emphysema alone.
Progressive disease is marked by the development of pulmonary hypertension, sometimes leading to cardiac failure.
Discuss asthma.
Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or early in the
morning.
The hallmarks of asthma are intermittent, reversible airway obstruction; chronic bronchial inflammation with eosinophils; bronchial smooth muscle cell hypertrophy and hyperreactivity; and increased mucus secretion.
Sometimes trivial stimuli are sufficient to trigger attacks in patients, because of airway hyperreactivity.
Describe the pathogenesis of asthma.
Major factors contributing to the development of asthma include genetic predisposition to type I hypersensitivity (atopy), acute and chronic airway inflammation, and bronchial hyperresponsiveness to a variety of stimuli.
Asthma may be subclassified as atopic (evidence of allergen sensitization) or nonatopic.
In both types, episodes of bronchospasm may be triggered by diverse exposures, such as respiratory infections (especially viral), airborne irritants (e.g., smoke, fumes), cold air, stress, and exercise.
There also are varying patterns of inflammation—eosinophilic (most common), neutrophilic, mixed inflammatory, and pauci-granulocytic—that are associated with differing etiologies, immunopathologies, and responses to treatment.
The classic atopic form is associated with excessive type 2 helper T (TH2) cell activation.
Cytokines produced by TH2 cells account for most of the features of atopic asthma—IL-4 and IL-13 stimulate IgE production, IL-5 activâtes eosinophils, and IL-13 also stimulates mucus production.
IgE coats submucosal mast cells, which on exposure to allergen release their granule contents and secrete cytokines and other mediators.
Mast cell–derived mediators produce two waves of reaction: an early (immediate) phase and a late phase (Fig. 13.10):
The early-phase reaction is dominated by bronchoconstriction, increased mucus production, and vasodilation.
Bronchoconstriction is triggered by mediators released from mast cells, including histamine, prostaglandin D2, and leukotrienes LTC4, D4, and E4, and also by reflex neural pathways.
The late-phase reaction is inflammatory in nature.
Inflammatory mediators stimulate epithelial cells to produce chemokines (including eotaxin, a potent chemoattractant and activator of eosinophils) that promote the recruitment of TH2
cells, eosinophils, and other leukocytes, thus amplifying an inflammatory reaction that is initiated by resident immune cells.
Repeated bouts of inflammation lead to structural changes in the bronchial wall that are collectively referred to as airway remodeling.
These changes include hypertrophy of bronchial smooth muscle and mucus glands and increased vascularity and deposition of subepithelial collagen.
Discuss atopic asthma.
This is the most common type of asthma and is a classic example of type I IgE–mediated hypersensitivity reaction.
It usually begins in childhood.
A positive family history of atopy and/or asthma is common, and the onset of asthmatic attacks is often preceded by allergic rhinitis, urticaria, or eczema.
Attacks may be triggered by allergens in dust, pollen, animal dander, or food, or by infections.
A skin test with the offending antigen results in an immediate wheal-and-flare reaction.
Atopic asthma also can be diagnosed based on serum radioallergosorbent tests (RASTs) that identify the presence of IgEs that recognize specific allergens.
Comparison of a normal airway and an airway
involved by asthma.
The asthmatic airway is marked by accumulation of mucus in the bronchial lumen secondary to an increase in the number of mucus-secreting goblet cells in the mucosa and hypertrophy of submucosal glands.
intense chronic inflammation due to recruitment of eosinophils, macrophages, and other
inflammatory cells
thickened basement membrane; and hypertrophy and hyperplasia of smooth muscle cells.
(C) Inhaled allergens (antigen) elicit a TH2-dominated response favoring IgE production
and eosinophil recruitment.
(D) On re-exposure to antigen (Ag), the immediate reaction is triggered by Ag-induced
cross-linking of IgE bound to Fc receptors on mast cells.
These cells release preformed mediators that directly and via neuronal reflexes induce.
bronchospasm, increased vascular permeability, mucus production, and recruitment of
leukocytes.
(E) Leukocytes recruited to the site of reaction (neutrophils, eosinophils, and basophils.
lymphocytes and monocytes) release additional mediators that initiate the late phase of
asthma.
Several factors released from eosinophils (e.g., major basic protein, eosinophil cationic
protein) also cause damage to the epithelium.
Discuss non-atopic asthma.
Patients with nonatopic forms of asthma do not have evidence of allergen sensitization, and skin test results usually are negative.
A positive family history of asthma is less common.
Respiratory infections due to viruses (e.g., rhinovirus, parainfluenza virus) and inhaled air pollutants (e.g., sulfur dioxide, ozone, nitrogen dioxide) are common triggers.
It is thought that virus-induced inflammation of the respiratory mucosa lowers the threshold of the subepithelial vagal receptors to irritants.
Discuss drug induced asthma and occupational asthma.
Several pharmacologic agents provoke asthma, aspirin being the most striking example.
Patients with aspirin sensitivity present with recurrent rhinitis, nasal polyps, urticaria, and bronchospasm.
Occupational Asthma
Occupational asthma may be triggered by fumes (epoxy resins, plastics), organic and chemical dusts (wood, cotton, platinum), gases (toluene),
and other chemicals.
Asthma attacks usually develop after repeated exposure to the inciting antigen(s).
Outline clinical features of asthma.
An attack of asthma is characterized by severe dyspnea and wheezing due to bronchoconstriction and mucus plugging, which leads to trapping of air in distal airspaces and progressive hyperinflation of the lungs.
In the usual case, attacks last from 1 to several hours and subside either spontaneously or with therapy.
Intervals between attacks are characteristically free from overt respiratory difficulties, but persistent, subtle deficits can be detected by pulmonary function tests.
Occasionally a severe paroxysm occurs that does not respond to therapy and persists for days and even weeks (status asthmaticus).
The associated hypercapnia, acidosis, and severe hypoxia may be fatal, although in most cases the condition is more disabling than lethal.
