Robbins Chapter 13: Lungs Flashcards
(101 cards)
1
Q
Bronchial Tree
A
Bronchi–>bronchioles—>terminal bronchioles—> respiratory bronchioles—>alveoli duct—> alveolar sacs
2
Q
Acinus
A
Respiratory bronchioles, alveolar ducts, alveolar sacs
3
Q
ARDS
A
Rest failure occurring within 1 week of a known clinical insult w. bilateral opacities on chest imaging, not fully explained by effusions, atelectasis, CF, or fluid overload.it is a restrictive airway disease
4
Q
ARDS symptoms
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Integrity of alveolar-capillary membrane is compromised by endothelial and epithelial injury. There is respiratory insufficiency, cyanosis, severe arterial hypoxemia that is refractory to oxygen therapy.
5
Q
Diffuse Alveolar Damage
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histological manifestation of ARDS in the lungs.
6
Q
Most frequent triggers of ARDS
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pneumonia, sepsis, aspiration, trauma, pancreatitis, transfusion reactions
7
Q
Acute Phase of ARDS
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Capillary congestion, necrosis of alveolar epithelial cells, interstitial and intra-alveolar edema hemorrhage, collections of neutrophils in capillaries. Presence of hyaline membrane lining alveolar ducts
8
Q
Organizing Stage of ARDS
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Type II pneumocytes proliferate to regenerate alveolar lining.
9
Q
Hyaline Membrane
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fibrin rich edema and necrotic epithelial cells, intra-alveolar fibrosis. Line the alveolar ducts.
10
Q
Poor Prognosis of ARDS
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Advanced age, multi organ failure, bacteremia
11
Q
Obstructive Airway Disease
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Increase resistance to airflow caused by partial or complete obstruction at any level.
12
Q
Restrictive Pulmonary Disease
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Reduced expansion of lung parenchyma and decreased total lung capacity.
13
Q
Types of obstructive disorders
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- Emphysema
- Asthma
- Chronic Bronchitis
- Bronchiectasis
14
Q
FEV1/FVC ratio in Obstructive disorders
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FEV1/FVC ration is reduced. FEV1 is reduced and FVC is reduced or unchanged.
15
Q
FEV1/FVC ration in Restrictive disorders
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FEV1/FVC remains unchanged. FVC is reduced and FEV1 remains unchanged or is reduced proportionally.
16
Q
Chronic Bronchitis initially affects..
A
the large airways
17
Q
Emphysema affects..
A
the acinus.
18
Q
COPD includes
A
chronic bronchitis and emphysema. It is irreversible
19
Q
Emphysema
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Permanent enlargement of air spaces distal to terminal bronchioles, accompanied by destruction of their walls without significant fibrosis.
20
Q
Lobule
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A cluster of 3-5 acinus
21
Q
4 major types of emphysema
A
- Centriacinar/Centrilobular
- Panacinar
- Distal Acinar
- Irregular
Only Centriacinar and panacinar cause significant airway obstruction.
22
Q
Centriacinar/Centrilobular Emphysema
A
Respiratory bronchioles are affected and distal alveoli are spared. More severe in apical segments of upper lobes. More common in cigarette smokers.
23
Q
Panacinar/Panlobular Emphysema
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All of acinus is affected. More severe in lower lobes. Associated with alpha1-antitrypsin deficiency.
24
Q
Distal Acinar/Paraseptal Emphysema
A
Distal part of acinus is abnormal. It occurs adjacent to areas of fibrosis & is more severe in upper half of lungs. More often present in young adults with spontaneous pneumothorax.
25
Irregular Emphysema
Irregular portions of acinus affected. Associated with scarring. Asymptomatic and maybe the most common form of emphysema.
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Pathogenesis of Emphysema
1. Inflammatory cells & mediators
2. Protease-antiprotease imbalance
3. Oxidative stress
4. Airway infection
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Inflammatory cells & mediators in Pathogenesis of Emphysema
Imflamm mediators increase (e.g. leukotriene B4, IL-8, TNF, etc) - they attract more inflammatory cells in circulation, amplify inflammatory process, & induce structural changes w. growth factors.
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Inflammatory cells present in emphysema lesions
Neutrophils, Macrophages, CD4+, CD8+ T cells
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Protease-Antiprotease Imbalance
Proteases released from inflammatory cells & epithelial cells that break down CT. In Pts that Deve,op emphysema there is a deficiency of anti-proteases.
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Oxidative Stress
ROS are generated from cigarette smoke & released from activated inflammatory cells (macrophages & neutrophils). Cause tissue damage.
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Airway infection in emphysema
Bacterial and/or viral infections can exacerbate emphysema
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Alpha1-antitrypsin
Present in serum, tissue fluid, macrophages. Inhibitor of proteases (particularly elastase) secreted by neutrophils during inflammation.
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Proteinase Inhibitor (Pi)
locus on chromosome 14 that encodes for Alpha1-antitrypsin.
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Protease mediates damage of...
Extracellular matrix.
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Small airways held open by...
elastic recoil of lung parenchyma. Loss of elastic tissue in walls of alveoli that surround respiratory bronchioles reduces radial traction and causes respiratory bronchioles to collapse during expiration.
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In emphysema there is loss of..
alveoli and alveolar capillaries.
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First symptom in Emphysema
Dyspnea
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FEV1/FVC ratio in Emphysema
Reduced, FEV1 reduced, FVC normal or reduced.
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Pink Puffers
Name for emphysema patients. Puffers due to dyspnea and hyperventilation, Pink because they are well oxygenated w. Hb.
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Classic presentation of emphysema w. no bronchitic component
Pt is barrel chested & dyspneic, thin, prolonged expiration, sitting forward in a hunched over position.
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Chronic Bronchitis Presentation
Dyspnea less prominent, hypoxia, cyanosis. Pts are obese
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Compensatory emphysema
Dilation of residual alveoli n response to loss of lung substance elsewhere
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Obstructive Overinflation
Expansion of lungs during air trapping
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Bullous Emphysema
Emphysema that produces large subpleural blebs (spaces >1 cm in diameter in the distended space). Blebs can rupture and lead to pneumothorax.
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Mediastinal/Interstitial Emphysema
Caused by entry of air into interstitial of lungs from where it can track to mediastinum & sometimes subcutaneous tissue.
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Chronic Bronchitis Diagnosis
It is diagnosed clinically: presence of persistent productive cough for at least 3 consecutive months in at least 2 consecutive years.
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Early stages of Chronic Bronchitis
Cough raises mucoid sputum but airflow is not obstructed.
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Distinctive feature of chronic bronchitis
Hyper-secretion of mucus, beginning in the large airways. Environmental irritants induce hypertrophy of mucus glands in the trachea and bronchi as well as increase in mucin secreting goblet cells in epithelial surfaces of smaller bronchi and bronchioles.
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Causes of Chronic Bronchitis
Cigarette smoking (most common), air pollutants (e.g. sulfur dioxide, nitrogen dioxide). Irritants cause inflammation w. infiltration of macrophages, neutrophils, & lymphocytes. No eosinophils present.
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Airflow obstruction in Chronic bronchitis results from
1) small airway disease, induced my mucus plugging of bronchiolar lumen, inflammation, & bronchiolar wall fibrosis
2) coexistant emphysema
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Mucin gene
transcribed in bronchial epithelium which produces neutrophil elastase (increased as a consequence to cig smoke)
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Morphology of Chronic Bronchitis
Mucosal lining of large airways is hyperemic and swollen by edema fluid and is covered by a layer of mucinous or mucopurulent secretions.
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Diagnostic feature of chronic bronchitis
enlargement of mucus secreting glands.
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Chronic Bronchiolitis (Small airway disease)
Characterized by goblet cell metaplasia, mucus plugging, inflammation, and fibrosis
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Bronchiolitis obliterans
Complete obliteration of the lumen as a consequence of fibrosis. Can be seen in chronic bronchitis
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Clinical features of chronic bronchitis
Course is variable. sputum production persist indefinitely w.o ventilatory dysfunction while others develop COPD w. significant outflow obstruction marked by hypercapnia, hypoxemia, and cyanosis.
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Progressive Chronic Bronchitis
Development of pulmonary HTN, can lead to heart failure, recurrent infections, and ultimately respiratory failure.
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Asthma
Chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and early in the morning.
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Hallmarks of asthma
intermittent, reversible airway obstruction, chronic bronchial inflammation w. eosinophils, bronchial smooth muscle cell hypertrophy and hyperactivity, and increased mucus secretion.
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Cells involved in asthma inflammatory response
eosinophils, mast cells, macrophages, lymphocytes, neutrophils, and epithelial cells.
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Hygiene hypothesis
lack of exposure to infectious organisms in early childhood results in defects in immune tolerance & hyperactivity to immune stimuli later in life.
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Factors contributing to development of asthma
Genetic predisposition to type I hypersensitivity (atopy), acute and chronic airway inflammation, bronchial hyper responsiveness to stimuli.
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Subclasses of Asthma
Atopic and nontoxic
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Bronchospasm in asthma triggered by
Resp infections (esp viral), airborne irritants, cold air, stress, exercise.
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Patterns of inflammation in asthma
Eosinophilic (most common), neutrophilic, mixed inflammatory, and pouch-granulocytic.
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Atopic Asthma
Most common type of asthma and is an example of type I IgE-mediated hypersensitivity reaction. Usually begins in childhood. Associated w. excess Th2 cell activation. Cytokines produced by Th2 cells account for most of the features of atopic asthma.
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cytokines produced by TH2 cells
IL-4 IL-13 (stimulate IgE production) and IL-5 (activates eosinophils); IL-13 stimulates mucous production
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Mast cell derived mediators produce 2 waves of a reaction
Early (immediate) phase and late phase
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Early Phase reaction in Mast cell mediated asthma
dominated by bronchoconstriction, increased mucus production, and vasodilation.
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Bronchoconstriction mediated by
mediators released from mast cells such as histamine, prostaglandin D2, leukotriene LTC4, D4, and E4, and reflex neural pathways
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Late phase reaction in Mast Cell Mediated Asthma
Inflammatory in nature. Inflammation mediators stimulate epithelial cells to produce chemokines that promote recruitment of TH2 cells, eosinophils, leukocytes.
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Airway remodeling In asthma
Occurs with recurrent bouts of inflammation in bronchial wall. Hyperthrophy and/or hyperplasia of bronchial smooth muscle and mucus glands and increased vascularity, thickening of airway wall, sub-basement membrane fibrosis, goblet cell metaplasia.
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Onset of asthmatic attacks in atopic asthma can be preceded by
allergic rhinitis, urticaria, or eczema. Attacks may be triggered by allergens in dust, pollen, animal dander, food, or by infections.
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Diagnosis of Atopic Asthma
Serum radioallergosrobent tests (RASTs) that identify the presence of IgEs that recognize specific allergens.
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Wheal and Flare reaction
Skin test w. offending allergen, positive in atopic asthma
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Non-atopic asthma
No allergen sensitization, skin results negative. Rest infections due to viruses (e.g. rhinovirus, parainfluenza virus) & inhaled pollutants (e.g. sulfur dioxide, ozone, nitrogen dioxide) are common triggers. Thought that virus induced inflammation of resp mucosa lowers the threshold of sub epithelial vagal receptors to irritants.
77
Drug induced asthma
caused by pharmacological agents, aspirin can cause asthma.
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Aspirin induced Asthma
recurrent rhinitis, nasal polyps, urticaria, and bronchospasm. can be due to decreased prostaglandin synthesis and increased leukotriene synthesis.
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Occupational asthma
can be triggered by fumes (epoxy, resins, plastics), organic and chemical dusts (wood, cotton, platinum), gases (toluene), etc.
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Asthma Morphology
Overinflated lungs bc of air trapping, occlusion of bronchi and bronchioles by thick, tenacious mucous plus containing whorls of shed epithelium (Cruschmann spirals). Numerous eosinophils & Charcot-Leyden crystals (crystals made of eosinophil protein)
81
Asthma Attack
dyspnea, wheezing due to bronchoconstriction and mucus plugging, which leads to trapping of air in distal airspaces & progressive hyperinflation of lungs. Can last from 1 to several hours and subside spontaneously or w. therapy.
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Status Asthmaticus
Severe asthma attack that does not respond to therapy and persists for days or weeks. Associated hypercapnia, acidosis, and hypoxia can be fatal.
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Asthma therapy
anti-inflammatory drugs (esp glucocorticoids) & bronchodilators/leukotriene inhibitors.
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Leukotrienes
potent bronchoconstrictors
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Eosinophils
Key inflammatory cells found in almost all subtypes of asthma, their products (major basic protein) are responsible for airway damage.
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Bronchiectasis
Permanent dilation of bronchi and bronchioles caused by destruction of smooth muscle and elastic tissue, typically results from chronic necrotizing infections. It is not a primary disorder as it occurs secondary to persistent infection/obstruction. Symptoms include cough and expectoration of purulent sputum. May complicate atopic asthma and chronic bronchitis.
87
Conditions predisposing to bronchiectasis
1. Bronchial obstruction
2. Cystic Fibrosis: obstruction caused by viscid fluid & secondary infections.
3. Immunodeficiency states (esp Ig deficiency) where there is recurrent bacterial infections.
3. Primary ciliary dyskinesia
4. Necrotizing/suppurative pneumonia
88
Primary ciliary dyskinesia
Also called immotile cilia syndrome: Rare AR disorder associated w. bronchiectasis & sterility in male. impaired cilia impairs mucociliary clearance of airways---recurrent 2infections.
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2 process that contribute to bronchiectasis
1. Infection
| 2. Obstruction
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Morphology of Bronchiectasis
It affects the lower lobes bilaterally usually, and air passages that are more vertical. When tumor or foreign body obstruction involvement may be localized to one segment of the lungs. Airways may be dilated to as much as 4 times their usual diameter & can be seen on gross examination almost to pleural surface.
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Clinical Features of Bronchiectasis
Severe, persistent cough associated w. expectoration of mucopurulent, sometimes fetid sputum. Other symptoms: dyspnea, rhino sinusitis, and hemoptysis. Symptoms are episodic, can lead to hypoxemia, hypercapnia, Pulmonary HTN, and for pulmonale.
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Chronic Interstitial Diseases (Restrictive/Infiltrative)
Bilateral, often patchy, pulmonary fibrosis affecting the walls of alveoli. There is reduced compliance (stiff lungs) that causes dyspnea. Bc of damage to alveolar epithelium & interstitial vasculature there is abnormal ventilation-perfusion ratio, leading to hypoxia. CXR shows small nodules, irregular lines, and ground glass shadows. May progress to resp failure, pulmonary HTN, & cor pulmonale. Results in diffuse scarring and gross destruction of lungs-- "end stage" or "honey-comb" lung.
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Categories of Interstitial Lung Disease
1. Fibrosing
2. Granulomatous
3. Eosinophilic
4. Smoking-related
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Fibrosing Interstitial Diseases
Usual Interstitial Pneumonia/Idiopathic pulmonary fibrosis, Nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, collagen vascular disease-associated, pneumoconiosis, therapy-associated (drugs, radiation)
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Granulomatous Interstitial Disease
Sarcoidosis + Hypersensitivity pneumonia
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Eosinophilic Interstitial Disease
Loeffler syndrome, drug allergy-related, idiopathic chronic eosinophilic pneumonia
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Smoking related interstitial disease
Desquamative interstitial pneumonia, respiratory bronchiolitis
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Idiopathic Pulmonary Fibrosis
pulmonary disorder of unknown etiology that is characterized by patchy progressive bilateral interstitial fibrosis. Also known as cryptogenic fibrosing alveolitis. Males affected more than female, occurs before age 50. Histological pattern is "usual interstitial pneumonia. Similar pathologic changes can be seen in asbestosis, collagen vascular disease, etc.
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Pathogenesis of IPF
Repeated injury & defective repair of alveolar epithelium often in genetically predisposed individual. Germ line mutations leading to loss of telomerase associated with increased risk. Fibroblastic/myofibroblastic proliferation-- fibroblastic foci.
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MUC5B gene
gene in which genetic variant may alter mucin production (involved in IPF)
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Morphology of IPF
Cobblestone pleural surfaces of lungs due to retraction of scars along interlobular septa. Firm rubbery, white areas of fibrosis, occurs preferentially along lower lobes, sub pleural regions and interlobular septa. Patchy interstitial fibrosis, varying in intensity & worsens with time.
