patoloji-ders-notlari

Asthma and Bronchiectasis

Serdar Balcı

Asthma and Bronchiectasis

Serdar BALCI, MD

Asthma

• Chronic inflammatory disorder of the airways
• Recurrent episodes of wheezing, breathlessness, chest tightness
• Cough at night and/or early in the morning
• Difficulty in expiration
  • Progressive hyperinflation of the lungs
  • Air trapped distal to the bronchi

Intermittent and reversible airway obstruction

Chronic bronchial inflammation with eosinophils

Bronchial smooth muscle cell hypertrophy and hyperreactivity

Increased mucus secretion

• Stimuli that trigger attacks in patients would have little or no effect in persons with normal airways

• Inflammatory response

  • Eosinophils, mast cells, macrophages, lymphocytes, neutrophils, epithelial cells

• Significant increase in the incidence of asthma in the Western world

  • Hygiene hypothesis
  • Eradication of infections may alter immune homeostasis
  • Promote allergic and other harmful immune responses

• Atopic

  • Evidence of allergen sensitization
  • History of allergic rhinitis, eczema

• Nonatopic

• Episodes of bronchospasm triggered by

  • Respiratory infections, viral
  • Environmental irritants, smoke, fumes
  • Cold air
  • Stress
  • Exercise

• Different patterns of inflammation

  • Eosinophilic
  • Neutrophilic
  • Mixed inflammatory
  • Pauci-granulocytic

• Genetic predisposition to type I hypersensitivity

  • Atopy

• Acute and chronic airway inflammation

• Bronchial hyperresponsiveness to a variety of stimuli

• Excessive TH2 reaction against environmental antigens

  • IL-4 stimulates IgE production
  • IL-5 activates eosinophils
  • IL-13 stimulates mucus production
  • IL-13 promotes IgE production by B cells

• IgE coats submucosal mast cells

  • Exposure to allergen → release granule contents

• Two waves of reaction

  • Early (immediate) phase
  • Late phase

Robbins Basic Pathology

Accumulation of mucus in the bronchial lumen

Increase in the number of mucus-secreting goblet cells

Basement membrane is thickened

Intense chronic inflammation

Eosinophils, macrophages,T H 2 lymph

Smooth muscle cells hypertrophy and hyperplasia

Hypertrophy of submucosal glands

Robbins Basic Pathology

Inhaled allergens start T H 2-dominated response

IgE production

Eosinophil recruitment

Priming or sensitization

Robbins Basic Pathology

Reexposure

Immediate reaction

Antigen-induced cross-linking of IgE bound to IgE receptors on mast cells

Release preformed mediators

• Bronchospasm
  • Directly from mediators
  • Direct stimulation of subepithelial vagal receptors
• Vascular permeability
• Mucus production
• Recruit additional mediator-releasing cells from blood

Late Phase

• Leukocytes signals the initiation of the late phase
• Fresh round of mediator release from leukocytes, endothelium, epithelial cells
• Epithelial cells activated
  • Eotaxins
• Major basic protein, eosinophil cationic protein
  • From eosinophils
  • Damage to the epithelium

Robbins Basic Pathology

• Repeated inflammation lead to structural changes
  • Airway remodeling
• Hypertrophy
  • Bronchial smooth muscle
  • Mucus glands
• Increased vascularity
• Deposition of subepithelial collagen
• May occur several years before initiation of symptoms

Robbins Basic Pathology

Asthma

• Complex genetic disorder
• Multiple susceptibility genes interact with environmental factors
• Variation in the expression of genes
• Combinations of polymorphisms
  • Immune response
  • Tissue remodeling
• Long arm of chromosome 5 (5q)
  • Regulation of IgE synthesis
  • Mast cell and eosinophil growth and differentiation
  • IL13
    • Genetic polymorphisms linked with susceptibility to the development of atopic asthma
  • CD14
    • Single-nucleotide polymorphisms associated with occupational asthma
  • Class II HLA alleles
    • Tendency to produce IgE antibodies
  • β2-adrenergic receptor gene
  • IL-4 receptor gene
    • Atopy, total serum IgE level, and asthma
• 20q
  • ADAM-33
    • Regulates proliferation of bronchial smooth muscle and fibroblasts
    • Airway remodeling

Atopic Asthma

• Most common type
• Begin in childhood
• Classic example of type I IgE–mediated hypersensitivity reaction
• Family history is common
• Asthmatic attacks preceded by allergic rhinitis, urticaria, eczema
• Triggered by
  • Environmental antigens
    • Dusts, pollen, animal dander, foods
• Infections

Non-Atopic Asthma

• No evidence of allergen sensitization
• Skin test results usually are negative
• Family history is less common
• Triggered by
  • Respiratory infections due to viruses
    • Rhinovirus, parainfluenza virus
  • Inhaled air pollutants
    • Sulfur dioxide, ozone, nitrogen dioxide
• Virus-induced inflammation
  • lowers the threshold of the subepithelial vagal receptors to irritants
• Eosinophils are also common

Drug-Induced Asthma

• Aspirin sensitivity
  • Recurrent rhinitis, nasal polyps, urticaria, bronchospasm
  • Inhibits the cyclooxygenase pathway of arachidonic acid metabolism without affecting the lipoxygenase route
  • Leukotrienes are produced more → bronchial spasm

Occupational Asthma

• Stimulated by
  • Fumes
    • Epoxy resins, plastics
  • Organic and chemical dusts
    • Wood, cotton, platinum
  • Gases
    • Toluene

Asthma

• Lungs are overdistended
  • Overinflation
  • Small areas of atelectasis
• Occlusion of bronchi and bronchioles by thick, sticky mucous plugs

Markedly expanded lungs

Autopsy Pathology: A Manual and Atlas

Mucous plugs fill and occlude the bronchi

Autopsy Pathology: A Manual and Atlas

• Curschmann spirals
  • Mucous plugs contain whorls of shed epithelium
• Numerous eosinophils
• Charcot-Leyden crystals
  • Collections of crystalloids made up of eosinophil proteins
• Airway remodeling
  • Thickening of airway wall
  • Sub-basement membrane fibrosis
  • Increased vascularity in submucosa
  • Increase in size of the submucosal glands
  • Goblet cell metaplasia of the airway epithelium
  • Hypertrophy and/or hyperplasia of the bronchial muscle

sub-basement membrane fibrosis, eosinophilic inflammation, and smooth muscle hyperplasia

http://upload.wikimedia.org/wikipedia/commons/8/81/Curshman%27s_Spiral.jpg

http://upload.wikimedia.org/wikipedia/commons/1/19/Charcot-Leyden_crystals%2C_HE_1.jpg

BRONCHIECTASIS

Bronchiectasis

Permanent dilation of bronchi and bronchioles

• Caused by destruction of the muscle and the supporting elastic tissue
• Resulting from or associated with chronic necrotizing infections
• Not a primary disease
  • Secondary to persisting infection or obstruction caused by a variety of conditions
  • Acquired, congenital, hereditary conditions predispose to bronchiectasis

Bronchiectasis in bronchial obstruction

Tumors, foreign bodies, and occasionally impaction of mucus

Localized to the obstructed lung segment

Complicate atopic asthma and chronic bronchitis

Bronchiectasis in cystic fibrosis

Obstruction caused by the secretion of abnormally viscid mucus

Predisposing to infections of the bronchial tree

Robbins Basic Pathology

Cystic fibrosis

Extensive mucous plugging and dilation of the tracheobronchial tree

Robbins Basic Pathology

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Robbins Basic Pathology

Cystic fibrosis

• Autosomal recessive disease
• Mutations in the CFTR gene encoding transmembrane regulator
• Chloride ion transport
  • High salt concentrations in sweat
  • Viscous luminal secretions in respiratory and gastrointestinal tracts
  • Severe (ΔF508) → multisystem disease
• Cardiopulmonary complications
  • Most common cause of death
  • Pulmonary infections
    • Pseudomonads
  • Bronchiectasis
  • Right-sided heart failure
• Pancreatic insufficiency
• Infertility
  • Congenital bilateral absence of vas deferens
• Liver
  • Cirrhosis

Bronchiectasis in immunodeficiency

Immunoglobulin deficiencies

Increased susceptibility to repeated bacterial infections

Bronchiectasis in Kartagener syndrome

• Rare autosomal recessive disorder
• Cilia impair mucociliary clearance in the airways
  • Persistent infections
• Reduce the mobility of spermatozoa
  • Sterility in males

Bronchiectasis in infections

• Pneumonia
  • Necrotizing or suppurative pneumonia
  • Staphylococcus aureus or Klebsiella spp.
• Posttuberculosis bronchiectasis

Bronchiectasis

• Obstruction and chronic persistent infection
  • Either may come first
    • Normal clearance mechanisms are disturbed by obstruction → secondary infection
    • Chronic infection over time → damage to bronchial walls → weakening and dilation
• Affects the lower lobes bilaterally
  • Air passages that are most vertical
  • Affect single segment in tumors and foreign bodies
• Most severe involvement is found in the more distal bronchi and bronchioles.
• Airways may be dilated to as much as four times their usual diameter
  • Can be followed almost to the pleural surfaces
• In normal lungs
  • Bronchioles cannot be followed beyond a point 2 to 3 cm from the pleural surfaces
• Histologic findings vary with the activity and chronicity
  • An intense acute and chronic inflammatory exudate within the walls of the bronchi and bronchioles
  • Desquamation of lining epithelium
  • Extensive areas of ulceration
• Mixed flora can be cultured from the involved bronchi
  • Staphylococci, streptococci, pneumococci, enteric organisms, anaerobic and microaerophilic bacteria
  • In children Haemophilus influenzae and Pseudomonas aeruginosa
• Healing
  • Epithelium may regenerate completely
  • Abnormal dilation and scarring persist
  • Fibrosis of the bronchial and bronchiolar walls and peribronchiolar fibrosis
  • Necrosis destroys the bronchial or bronchiolar walls
  • Abscess cavity → Fungus ball
• Complications
  • Clubbing of the fingers
  • Hypoxemia, hypercapnia, pulmonary hypertension, rarely cor pulmonale
  • Brain abscesses
  • Reactive amyloidosis