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Pulmonary pathology copd

Pulmonary pathology copd






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    Pulmonary pathology copd Pulmonary pathology copd Presentation Transcript

    • Two major lung diseases 1. Obstructive – airway disease a) limitations of airflow i) partial or complete obstruction at any level major causes a) asthma – obstructive b) emphysema – loss of elastic recoil c) chronic bronchitis d) Bronchiectasis e) cystic fibrosis f) bronchiolitis www.freelivedoctor.com
      • 1. Obstructive (con’t)
      • In these diseases:
      • TLC and FVC are normal or slightly increased
      • Marked by decreased expiratory flow (FEV 1 )
      • Ratio of FEV 1 to FVC is decreased
      • Obstructive Lung Disease
      • 1. Asthma
      • “ Characterized by episodic, reversible bronchospasm resulting from broncho constriction in response to various stimuli”
      • a) basis of hyperactivity of bronchi is unclear
      • i) thought to be from persistent/chronic bronchial inflammation of the airways
      • - eosinophils
      • - mast cells, epithelial cells
      • - macrophages
      • - neutrophils, T-lymphocytes
    • b) clinically i ) dyspnea ii) cough iii) wheezing (expiratory) - triggered via bronchospasm iv) 5% adults and 10%children v) status asthmaticus – fatal outcome vi) between attacks  asymptomatic www.freelivedoctor.com
    • Classification a) extrinsic asthma – initiated by type I hypersensitivity reaction induced by exposure to extrinsic antigen b) 3 types of extrinsic asthma i) atopic (most common); 1st 2 decades; increased IgE; CD4 and T cells - type I hypersensitivity ii) occupational (many forms) iii) allergic bronchopulmonary aspergillus’s (bacterial colonization followed by IgE antibodies) www.freelivedoctor.com
      • Major etiologic factors of asthma
      • a) genetic predisposition to type I hypersensitivity (“atopy”)
      • i) precise cellular response is unknown
      • b) type 2 helper T (T H 2) cells are important components of bronchial inflammation
      • i) release cytokines (IL)
      • - promote inflammatory response
      • - stimulate B-cells to  IgE and other antibodies
      • c) (T H 1)  IFN-1  and IL-2
      • i) kill viruses, etc by activating macrophages and cytotoxic T cells
      • Both these two T cell types regulate one
      • another
      • a) imbalance between these may be the key to asthma
      • b) when IFN-1  is altered and fails to “check” T H 2  airway inflammation
      • i) patients with allergic asthma have increased T H 2
      • - etiology is unclear
      • ii) transcription factor T-bet is required for T H 1 cell differentiation
      • - asthmatics are deficient in this transcription factor
    • www.freelivedoctor.com
      • Airway remodeling
      • a) seen several years prior to onset of symptoms
      • i) ADAM-33 gene linkage to asthma
      • - found in bronchial SM
      • - found in lung fibrobalsts
      • ii) ADAM-33 polymorphism causes
      • - proliferation of bronchial SM cells and fibrobalst, thereby contributing to:
      •  bronchial hyperactivity
      •  subepithelial fibrosis
      • iii) Mast cells
    • iv) thickening of basement membrane v) edema vi)  size of submucosal glands vii) muscular hypertrophy viii) inflammatory infiltrate in bronchial walls (eosinophils and Mast cells) www.freelivedoctor.com
      • Atopic asthma
      • a) most common type of asthma
      • i) childhood
      • ii) triggered by environmental antigen
      • (dust, pollen, food, etc)
      • iii) positive family history is common
      • iv) attacks usually preceded by allergic rhinitis, utricaria or eczema
      • Proposed progression
      • a) sensitization to allergen in lung results in
      • b) T H 2 synthesis/activation 
      • c) release of cytokines (IL-4, IL-5) 
      • d) promote IgE by B-cells, growth of Mast cells (IL-4), and eosinophils (IL-5) 
      • e) “acute phase response” (4-8 hrs)
      • f) initial Mast cell reactions occur on mucosal surface  releasing mediators
      • i) opens mucosal tight junctions
      • - promotes antigen movement to mucosal Mast cells
      • ii) stimulation of parasympathetics
      • - bronchoconstriction
    • g) acute phase begins within minutes of exposure i) edema ii)  mucus secretion iii) hypotension (rare occurrence) h) Mast cells release other mediators i)  other leukocytes - neutrophils - lymphocytes - monocytes - basophils - eosinophils (mainly – IL-5) i) these inflammatory cells set stage for “late phase reaction” (12-24 hrs) www.freelivedoctor.com
      • Late phase reaction
      • a) induced by  leukocyte chemotaxis induced by Mast cells
      • b) other cells can also produce mediators
      • i) vascular endothelial cells
      • ii) airway epithelial cells
      • - produce cytokines in response to infections, drugs, gases.
      • - eotaxin  chemoattractant and activator of eosinophils
      • - basic protein of eosinophils causes epithelial damage  bronchoconstriction
    • www.freelivedoctor.com
      • Mediators
      • a) leukotrienes  C 4 D 4 E 4  bronchoconstriction,  vascular permeability,   mucus secretion
      • b) Ach  SM constriction (via muscarinic)
      • c) histamine PGD 2 PAF (serotonin)  bronchoconstriction
      • d) IL-1, TNF, IL-6, eotaxin, NO, endothelin
      • Nonatopic (i.e., intrinsic) asthma
      • a) usually triggered by respiratory viral infection (rhino-, parainfluenza)
      • b) family history uncommon
      • c) serum IgE are normal
      • d) no associated allergies
      • e) exercise
      • f) cold
      • Theory  hyperirritability of airways
      • a) virus lowers threshold of vagal receptors to irritants  bronchoconstriction
      • Occupational induced asthma
      • a) fumes (epoxy resins, plastic)
      • b) gases (toluene)
      • c) dust (wool, wood, platinum)
      • d) penicillin products
      • e) formaldehyde
      • Drug induced asthma
      • a) aspirin
      • Since so many patients have overlapping
      • characteristics and  IgE, this classification is
      • no longer clinically applicable.
      • Asthma developing early in life has strong
      • allergic (i.e., extrinsic) component, whereas
      • developing late in life more often intrinsic (i.e.,
      • nonatopic)
      • Clinical Course
      • a) labors to get air in and can’t exhale well
      • b) Bronchodilators and corticosteroids
      • Status asthmaticus – last days to weeks and
      • does not respond to therapy
      • a) hypercapnia
      • i) acidosis may be fatal
    • www.freelivedoctor.com
      • COPD
      • Affects more than 10% of US adult
      • population and is 4th leading cause of
      • death in US
      • Irreversible airflow obstruction of COPD
      • distinguishes it from asthma (largely
      • reversible)
      • Refer to emphysema and chronic
      • bronchitis (smoking common to both)
    • www.freelivedoctor.com
      • 2. Emphysema
      • Permanent enlargement of airspaces
      • distal to terminal bronchioles and is
      • accompanied by destruction of their
      • walls
      • Overinflation  enlargement of airspaces
      • w/no destruction
      • a) compensated overinflation due to contralateral pneumonectomy
      • Morphological definition (based on area
      • w/in lobule)
    • Types of emphysema a) Panacinar (panlobular) emphysema i) uniformly enlarged acini ii) lower lung zones iii)  1-antitrypsin definciency b) Centrilacinar emphysema i) dilation upstream with normal distal portions ii) more common than panacinar (~ 95% of cases) iii) more common/severe in upper lobes - contain black pigment www.freelivedoctor.com
    • Centriacinar (con’t) iv) in severe disease distal acini may be involved  differentialte from panacinar difficult v) seen in heavy smokers, often in association with chronic bronchitis c) Distal Acinar (paraseptal) emphysema i) proximal acini normal and distal part most involved ii) upper half of lungs/near pleura iii) associated with spontaneous pneumothorax in the young www.freelivedoctor.com
      • d) irregular
      • i) acini irregularly involved
      • ii) airspace enlargement with fibrosis
      • iii) may be the most common
      • - most autopsies show some scarring from healed inflammation
      • iv) most are asymptomatic and not clinically significant
      • Centriacinar and panacinar are the ones
      • that cause clinical airflow obstruction
    • www.freelivedoctor.com
      • Incidence
      • Common disease (~50% of patients on
      • autopsy) – asymptomatic
      • Centrilobular – most common and severe in
      • men
      • Clear association with cigarette smoking
      • 5th and 8th decade becomes disabling
      • Chronic mild inflammation of lung architecture
      • a) mediators
      • Centriacinar and panacinar
      • a) genesis not completely understood
      • b) 2 Theories
      • i) protease-antiprotease imbalance
      • ii) oxidant-antioxidant imbalance
      • Protease-antiprotease Hypothesis
      • a) patients with deficiency of antiprotease,  1-antitrypsin (AAT) have increased tendency to develop emphysema
      • b) about 1% of all patients have this defect
      • c)  1-antitrypsin major inhibitor of proteases, particularly elastase d) homozygous patients w/genetic AAT deficiency  develop emphysema
      • e) PiMM  normal phenotype for  1- antitrypsin
      • f) PiZZ  common phenotype for AAT deficiency
      • Sequence:
      • a) neutrophils (primary source of proteases) sequestered in pulmonary capillaries (lower zones primarily)
      • i) smoking  neutrophils & macrophages
      • ii) CD8+ T cells  cause direct damage and/or recruit macrophages
      • b) few gain access to alveolar space
      • c) release of proteolytic enzymes + ROS
      • d) low levels of  1-antitrypsin  damage to elastin (via elastase)
      • e) emphysema ensues
      • Oxidant-antioxidant hypothesis
      • Lung has antioxidants
      • a) superoxide dismutase
      • b) glutathione
      • Smoke has many oxidant species which
      • deplete these normal scavengers
      • a) activated neutrophils also has ROS
      • Oxidative injury depletes or destroys
      • native antiproteases
      • a) ”Functional”  1- antitrypsin definciency even though blood enzyme is not deficient
      • Smoking (ROS) and  1 - antitrypsin deficiency SEVERE DAMAGE!!!
      • Signs:
      • a) “Barrel” chested and dyspneic
      • b) Hyperventilation
      • c) Normal blood gases (- “pink puffers”)
      • Some patients have other pulmonary disease
      • a) do not hyperventilate and become cyanotic
      • i) “blue-bloaters” (chronic bronchitis)
      • b) death from Right CHF, coma, acidosis, pulmonary fatigue
      • Other
      • a) Obstructive overinflation
      • i) “ball valve” affect
      • ii) sub total obstruction by tumor, etc
      • iii) classic example:
      • - congenital lobar overinflation
      • - - hypoplasia?
      • b) Bullous
      • i) large subpleural blebs (> 1-2 cm dia)
      • ii) apical regions
      • iii) may cause pneumothorax
      • c) interstitial
      • i) air
      • - alveolar tears, etc.
    • www.freelivedoctor.com
      • Chronic Bronchitis
      • Common in smokers (> 90%), passive
      • inhalation of smoke and smog-ridden cities
      • Definition: Based on clinical grounds.
      • “ persistent productive cough for at least 3
      • consecutive months and at least 2 consecutive
      • years”
      • Occurrence: (Increased mucus production)
      • a) simple chronic bronchitis
      • i) raises mucoid sputum
      • ii) airflow not obstructed
      • b) chronic mucopurulent bronchitis
      • i) mucus and pus
      • ii) from secondary infection
      • c) chronic asthmatic bronchitis
      • i) bronchitis with intermittent hypersensitivity and asthmatic constriction (difficult to diagnose from atopic asthma)
      • d) chronic obstructive bronchitis
      • i) difficult outflow as measured by pulmonary function test
      • Involves large bronchioles
      • Small airway disease (bronchiolitis)
      • resulting from fibroses and inflammation
      • may lead to (chronic bronchitis)
        • a) increase goblet cells in small bronchi and bronchioles (i.e., bronchiolitis obliterans)
    • -
      • Pathogenesis
      • Hypersecretion of mucus
      • a) beginning in large airways
      • b) smoking single most important causative factor
      • Eosinophils are lacking
      • Increased transcription of mucin gene
      • (MUC5AC) by cigarette smoke
      • a) enlargement of mucus secreting glands (major consequence)
      • b) hyperplasia and hypertrophy of mucus secreting cells and increase proportion of mucus to serous secretions.
      • i) Reid index – size of mucus glands
      • Cough with sputum may last indefinitely
      • without respiratory obstruction
      • usually accompanies emphysema
      • Some patients develop COPD with
      • outflow obstruction
      • a) hypercapnia
      • b) hypoxemia
      • c) exertional dyspnea
      • d) cyanosis – “blue-bloaters”
      • Progression of disease
      • a) pulmonary hypertension (Cor Pulmonale)
      • b) cardiac failure
      • Metaplasia of bronchial epithelium
    • www.freelivedoctor.com
      • Bronchiectasis
      • Permanent dilation of bronchi and
      • bronchioles caused by destruction of the
      • muscle and elastic supporting tissue
      • resulting or associated with
      • chronic necrotizing infection.
      • Is not primary disease but secondary to
      • persisting infection or obstruction caused
      • by variety of conditions.
      • Cough and purulent sputum
      • Irreversible Bronchial dilation
      • Most often caused by:
      • a) bronchial obstruction
      • i) tumors
      • ii) foreign bodies
      • iii) localized to obstructed lung segment
      • b) congenital or hereditary condition
      • i) cystic fibrosis
      • ii) immunodeficiency states (IgE deficiency) – repeated infections
      • iii) Kartagener syndrome (Structural abnormalities of cilia (decreased mucocilliary clearance)
      • - Sterility in males/females
    • c) necrotizing pneumonia (S. aureus, K. pneumoniae) i) post tubercular bronchiectasis significant cause of morbidity www.freelivedoctor.com