COPD Flashcards
Individual disorders in COPD includes?
- Emphysema
- Chronic bronchitis
- Asthma
- Bronchiectasis
Emphysema is defined by ?
irreversible enlargement of the airspaces DISTAL to the terminal bronchiole associated with destruction of their walls without any obvious fibrosis
Definition of COPD
“a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities caused by exposure to noxious particles or gases.”
While asthma is distinguished from chronic bronchitis and emphysema by??
The presence of reversible bronchospasm
COPD and smoking?
Overall, 35% to 50% of heavy smokers develop COPD
conversely about 80% of COPD is attributable to smoking.
Emphysema epidemiology ??
- 4th leading cause of morbidity and mortality in the united state
- commoner in Women, African-Americans
- Associated with heavy cigarettes smoking
Classification of emphysema ?
Based on anatomic distribution within the lobule:
- Centriacinar
- Panacinar
- paraseptal (distal acini)
- irregular
Features of centriacinar emphysema ?
- Seen predominantly in heavy smokers
- Often associated with bronchitis affecting the apical lobes
- Distal alveoli are spared
- proximal respiratory bronchioles affected often with inflammation
Features of Panacinar enlargement ?
- Uniform enlargement from respiratory bronchioles to terminal alveoli
- Associated with a1 anti-trypsin deficiency
- tends to occur more commonly in the lower zones and in the anterior margins of the lung and it is usually most severe at the lung bases
Features of paraseptal emphysema (distal acini) ?
- Seen in *^pleural surfaces**
- Normal proximal acini
- Distal alveoli is affected
- Seen in Cases of spontaneous pneumothorax
- more severe in the upper half of the lungs.
Irregular emphysema?
- the acinus is irregularly involved,
- Associated with scarring
- Airspace enlargement with fibrosis
- clinically induced insignificant
Most common form of Emphysema is the?
Centriacinar emphysema (>95%)
Heavy smokers with COPD are at risk of having what type of emphysema?
Centriacinar Emphysema
α1-antitrypsin deficiency is associated with ?
Panacinar emphysema
Pathogenesis of emphysema
A) There’s activation of inflammatory cells (macrophages, CD8, CD4, T lymphocytes and neutrophils) reach release variety of mediators (leukotrienes B4, IL8, TNF) that sustain inflammatory process and lead to destruction of alveoli wall
B) Proteaseantiprotease hypothesis
C) imbalance of antioxidants and oxidants
Deficiency of antiprotease alpha 1 antitrypsin enables?
Unchecked destruction of elastic tissue thus emphysema results
80% of them will develop Panacinar emphysema
Clinical features of emphysema ?
Pink puffers - Well oxygenated but over ventilated
Dyspnea with prolonged expiration
Cough or wheezing
Expectoration
Weight
- Sits forward in a hunched over position and breaths through pursed lips
Diagnosis or emphysema ??
On examination, patient is barrel chested
Expiratory airflow limitation Pulmonary function tests show: decreased FEV1 (at 1sec) using a spirometer - Key to diagnosis
Morphological features of emphysema ?
Gross;
- Enlarged Lung with apical bullae or bleb
Histology;
Abnormally large alveoli with thin septa, having focal Centriacinar fibrosis and lots of inflammatory cells
Treatment of emphysema
- Bronchodilators
- Sterioids
- Surgery: bullectomy/ lung volume reduction
- lung transplantation
- substitution therapy with alpha 1- AT
Complications of emphysema ?
- Cor Pulmonale
- congestive heart failure
- right sided heart failure
Lung collapse secondary to pneumothorax - Death from respiratory acidosis
- coma
Chronic bronchitis is defined as?
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 is common among?
Habitual smokers
Dwellers of smog-Kaiden cities
Pathogenesis of chronic bronchitis
- Long standing irritation from inhaled tobacco smoke and dust from grain, cotton and silica
- Activation of mediators of inflammation within the large airway (proteases, elastase, cathepsin and matrix metalloproteinases) from neutrophils
- Then, mucus hypersecretion in the large airways and hypertrophy of submucosal glands in the trachea and bronchi
- As chronic bronchitis persists, there’s a marked increase in goblet cells of small airway
- leading to excessive mucus production that contributes to airway obstruction
Clinical features of chronic bronchitis ?
- Persistent cough productive of sputum
- Dyspnea on excertion develops
- Hyoercapnea
- Hypoxemia
- Mild cyanosis (blue bloaters)
Complications of chronic bronchitis ?
- Cor pulmonary
- Cardiac failure
- Death from impairment of respiratory function due to superimposed acute infections
- Malignancy from atypical metaplasia and dysplasia of the respiratory epithelium
Differences between Chronic bronchitis and emphysema ?
Age
CB: 40-45……….EM: 50-75
Dyspnea
CB: mild/late ………..EM; severe/early
Cough
CB; Early, copious sputum ……EM; Late, scanty sputum
infections
CB; common……EM: occasional
Respiratory insufficiency
CB; Repeated ….. EM; Terminal
Cor Pulmonale
CB; common ……. EM; Rare, Terminal
Airways resistance
CB; increased…… EM: Normal/slightly increased
Elastic recoil
CB; Normal …… EM; Low
Chest radiograph
CB: Prominent large vessels, large heart
EM; Hyperinflation, small heart
Appearance
CB: Blue bloater ……..EM: Pink puffers
Asthma is defined as?
Reversible inflammatory lung disorder characterized by
- Recurrent episode of wheezing
- Breathlessness
- Chest tightness
- Cough
Especially at night/early Morning
Classification if Asthma
1) based on known allergen - Atopic & Non Atopic
2) pattern of airway inflammation -
- Eosinophilic
- Neutrophilic
- mixed inflammatory
- Pauci-granulocytic asthma
3) Bronchoconstriction trigger
- Seasonal
- excercise induced
- Drug induced
- Occupational asthma
- Asthmatic Bronchitis in smokers
Etiology of asthma
- Genetic predisposition to type 1 hypersensitivity and environmental allergens
- Respiratory infections (viral esp)
- Environmental Exposure to irritants (smoke, fumes )
- Cold air
- Stress
- Exercise
The clinical features of asthma are due to?
1) increased airway response to variety of stimuli —- episodic brinchoconstriction
2) Imflammation of the bronchial walls
3) increased Mucus secretion
Atopic asthma ?
-Type 1 igE mediated hypersensitivity reaction
-triggers; Dusts, Pollens, roach, animal dander, food
- positive family history of asthma commonly
- Skin test with the offending antigen elicit an immediate wheel and flare reaction
Atopic asthma is diagnosed how??
Based on evidence of allegations ergen sensitization by se rum radiolallergosorbent tests (RAST)
Rasts identifies the presence of IgE specific for a penal of alkwrgukenb
Non-atopic asthma?
- No evidence of allergen sensitization
- Skin tests are usually negative
- Positive Family Hx is less common
- hyper irritability is due to trigger by viral infections (rhinovirus) and parainfluenza virus
I’m the pathogenesis of atopic asthma, what’s the function of each cytokines secreted by TH2 cells?
IL4 - production of IgE
IL5 - Activates locally recruited eosinophils
1L13 - stimulates mucus secretion from bronchial submucosal glands & IgE production by B cells
- IgE coats submucosal mast cells
Coating of Submucosal mast cells by IgE causes what?
Upon repeat allergen exposure, mast cells trigger the release of granule contents like cytokines, mediators which induces ;
1) Early phase; immediate hypersensitivity reaction
2) late phase reaction.
The early phase of Ashhma includes ?
1) Bronchocontriction; stimulation of vagal receptors (parasympathetic)
2) increased mucus production
3) variable degree of vasodilation with increased vascular permeability
The late phase of the pathogenesis of Asthma. Include?
- Inflammation with leucocyte recruitment
- Eotaxin from airway bronchial cells (potent chemoattractant and activator if eosinophil which cause epithelial damage and more sissy constrictions.
Due to repeated bouts of antigen exposure and immune reactions, the bronchial walk undergoes?
**Airway remodeling *
- hypertrophy and hyperplasia of bronchial smooth muscle
- epithelial injury
- increased airway vascularity
- increased subepithelial mucus gland (hypertrophy/hyperplasia)
- sub-epithelial collagen deposit
Genetics of asthma involves what chromosome and encondings?
Mutations in chromosome 5q loci encoding IL3, IL4, IL5, IL9, IL13, IL14 receptors
Receptor for LPs CD14 gene
B2 adrenergic receptors
Chitinase family (YKL-40)
ADAM 33 polymorphism in ASTHMA does what?
Enhances bronchial hypersensitivity and subepithelial fibrosis
Most implicated genes in ASTHMA are ?
Polymorphisms in
- IL13 gene
- CD14 gene
Clinical features
Chest tightness
Dyspnea
Wheezing
Cough w/wo sputum production
Cyanosis in severe cases and even death
Gross features of Asthmatic lungs
Thick tenacious mucus plug blocking the bronchi and bronchioles
In status epilepticus patients what do you see in their lungs ?
Hyperinflated lungs with atelectasis
Histological features of the lungs of an asthmatic patients
Curschmann spirals
charcot-leyden crystals and numerous eosinophils
Blockage of the duct of the subepithelial mucus glands forms what?
Curschmann spirals
Airway remodeling includes ?
- Overall thickening of the airway wall
- Sub-basement membrane fibrosis due to deposit of collagen 1 and 3
- increased vascularity
- hypertrophy of submucosal glands and mucous metaplasia of airway epithelial cells
- hypertrophy and hyperplasia of the bronchial wall muscles
FBC in asthmatic patients shows?
Elevated eosinophils
Treatment of asthma include ?
- Bronchodilators
- B2 adrenergic receptor antagonist
- surgery; bronchial thermoplasty
Bronchiectasis is defined as?
Irreversible Dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue, resulting from or associated with chronic necrotizing infections
Bronchiectasis is associated with what disease ?
- Cystic fibrosis
- intralobar sequestration of the lungs
- Immunodeficiency states
- Primary ciliary Dyskinesia
- kartagener syndrome
Post infectious conditions that can cause Bronchiectasis include ?
Mycobacterium tuberculosis
Staphylococcus aureus
Hemophilus influenzae
Pseudomonas
Adenovirus, influenza virus, HIV
Aspergillosis
Other conditions associated with Bronchiectasis ?
Tumor, foreign body aspiration
Mucus impaction
Rheumatoid arthritis
SLE
IBD
Post transplantation (lung rejection, chronic graft versus host disease after bone marrow transplant)
Pathogenesis of Bronchiectasis
Caused by infection or obstruction
- impairment of clearing mechanisms
- pooling of secretions distal to obstruction and inflammation
- necrosis, fibrosis and dilatation of airways
CF in Bronchiectasis
- primary defect of ion transport (defective mucocillairy mechanism )
- thick viscous secretions accumulates and obstruct airways
- increased susceptibility of bacterial infection and further damage to airways
- widespread damage to airway walls
- destruction of supporting smooth muscle and elastic tissue
- fibrosis
- further dilatation of bronchi
- brochiolitis obliterans; obliteration of the smaller bronchioles by fibrosis
Primary ciliary dyskinesia in Bronchiectasis
- Poor functioning cilia contributing to retention of secretions ?
- recurrent infections ultimately leading to Bronchiectasis
- absence of shortening of dynein arms
- coordinated bending of the cilia is lost
- associated with kartagener syndrome, sinusitis, Bronchiectasis, situs invertus ( partial ateralizing abnormality)
- cell motility is affected in embryodnesis leading to situs inversus
- infertile male due to sperm dysmotility
Gross and microscopic description of PCD?
Gross
- Affects the lower lobes bilaterally
- Airways are dilated (X4)
- Cyst filled bronchi with mucopurulent secretion
Microscopy
- may show acute and chronic inflammatory education within bronchioles and bronchi wall
- may show extensive areas of necrotizing ulceration,
- lung abscess or fibrosis
Complications of PCD ?
- Obstructive respiratory insufficiency
- Marked Dyspnea and Cyanosis
- cor Pulmonale
- Brain abscess
Clinical features of PCD?
Severe persistent cough
Foul smelling sputum/ Bloody sputum
Dyspnea
Orthopnea
hemoptysis
- Episodic symptoms, precipitated by URTI,
- paroxysms of cough when patients rises in the morning or changes position
