lecture notes

• 3.06: Pathology Of Asthma & COPD
• MED 601
• Mobile- 9215131
• Blood Supply of Lung

  • Dual supply: pulmonary & bronchial arteries
  • Pulmonary arteries- deoxygenated blood
  • Branches with bronchial system
  • Elastic type vessels
  • Caliber remain same during cardiac cycle
  • Pressure is low
  • Bronchial: oxygenated blood for bronchial system
  • High pressure- branch from aorta
  • Lymphatic drainage
• Trachea


  • Pseudo stratified ciliated epithelium with Goblet cells
  • loose vascular Connective Tissue
  • Submucosa
  • Sero-mucous glands
  • Cartilage ring
  • Adventitia
• Tertiary Bronchus


  • Tall columnar epithelium reduced Goblet cells
  • LP- thin, elastic with circular muscle layer
  • - sparse Sero-mucous glands
  • C- few irregular plates of cartilage, start disappearing
• Bronchiole


  • Airway < 1mm in size
  • Simple columnar or cuboidal epithelium
  • Few goblet cells
  • Circular Smooth muscle
  • Regulate air flow in lung
• ASTHMA


  • episodic disease of the airways
  • characterized by increased responsiveness of tracheobronchial tree to a variety of stimuli
  • resulting in widespread spasmodic narrowing of the air passages
  • may be relieved spontaneously or by therapy
  • clinically manifested by paroxysms of dyspnea
  • cough
  • wheezing
  • severe & unremitting form: status asthmatics
  • may prove fatal
• Bronchial Asthma Types


  • Extrinsic / Atopic / allergic
  • Non-atopic/non-allergic/idiosyncratic
• 1. Extrinsic/Atopic /Allergic Asthma

  • induced by inhaled antigens
  • begins in childhood & reducing with increasing age
  • positive family history of allergies
  • Other allergic disorders associated
  • environmental allergens
  • Seasonal- Pollens , flowers, food
  • Non seasonal- dust , pet feathers, dandruff, excreta , food, fungus
  • Atopic Triad: Asthma
  • Samter's triad: Asthma
  • Atopic dermatitis/ eczema
  • Nasal polyp
  • Atopic rhinitis
  • aspirin sensitivity
• 1. NON ATOPIC ASTHMA


  • hyperirritability of bronchial tree
  • low threshold of sub-epithelial vagal receptors
  • air pollutants- sulphur dioxide, ozone, NO2, smoke
  • Common triggers- virus/ RTI
  • cold air
  • stress
  • heavy exercise
• 1. NON ATOPIC ASTHMA : INFECTIOUS ASTHMA

  • common precipitating factor in childhood asthma
  • respiratory tract infection by virus: rhinovirus
  • influenza
  • parainfluenza
  • Inflammatory responses
  • Cause: Persistent bronchial hyper reactivity
• 1. NON ATOPIC ASTHMA : EXERCISE-INDUCED

  • asthmatic or normal case
  • Associated: magnitude of heat
  • water loss from airways
  • rapid ventilation (severity of exercise)
  • colder & dry air breathed in
  • mechanisms – unclear
  • mediator release
  • vascular congestion
  • at rewarming of airways after exertion
• DRUG INDUCED ASTHMA

  • Usually in known asthmatic patients
  • Sensitive to aspirin & other NSAD
  • NSAD- inhibit cyclooxygenase pathway
  • not affecting the lipoxygenase route
  • Beta –Adrenergic antagonists
  • Causes - bronchoconstriction
• Occupational Asthma

  • Fumes & gases: epoxy resins, plastics, toluene
  • organic – wood, cotton , grain , flour
  • chemical – dyes , organic compounds
  • formaldehyde, petroleum products
  • Colour & preservatives used in- food, industries , drugs
  • Biologic enzymes- laundry powder
  • insects & animal excreta
  • after repeated exposure- Ig E formation
  • Stimulation & over activity of Autonomic NS
  • organic phosphorus insecticides- act as anticholinesterases
• EMOTIONAL FACTORS

  • In asthmatics
  • Psychological stress
  • Aggravate or precipitate
  • Vagal efferent stimulation
  • Environmental Hygiene hypothesis
  • - in late onset of asthma
• Antigen presenting cell

  • B-L
  • Dendritic
  • Macrophage
• Type I hypersensitivity Reaction

  1. Repeat exposure to Ag

  2. Antigen specific IgE molecules

  3. IgE attach to Fc receptors on mast cell

  4. Cross linking of IgE molecules

  5. MHC II

  6. Histamine

  7. Leukotriene

  8. IL4

  9. IL 5

  10. Leukotrienes Proteases

  11. Tissue damage

  12. Chromosome 6

  13. Bronchospasm
• Cytokines

  • Vasoactive amines & lipid mediators
• 1. 10 Hrs
• Mast Cell (Revision- year 1)

  • Origin- bone marrow by myeloid precursors
  • reside in connective tissues
  • TH2 & mast cells release mediators
  • histamine
  • Bradykinin
  • Leukotriene
  • Prostaglandins
  • Thromboxane A2
  • platelet-activating factor (PAF)
  • cytokines – IL- 4 & IL-5
• immediate hypersensitivity

  • smooth muscle contraction
  • mucous secretion
  • increased vascular permeability
  • edema
• Chemotactic factors

  • attract N, E & platelets
  • eosinophil granules
  • - cationic protein
  • - impairs mucociliary function
  • - damages epithelial cells
  • stimulate nerve endings in mucosa
  • autonomic discharge
• Asthma

  • Cough productive- mucus
  • Tightness of chest/ difficulty in breathing- narrow airway
  • SOB
  • speaking difficulty
  • Accessory muscles of respiration
  • Obstructive lung disease- air trapped leading to hyper resonance on percussion
  • 7-Wheezing on expiration – increased resistance due to mucus
  • narrow bronchus
  • FVC reduced
  • FEV1 markedly reduced
  • FEV1/ FVC= < 75 % in obstructive condition
• Chronic Asthma

  • airway remodelling
  • Thick bronchial wall
  • BM thickening- Collagen deposition
  • increased vascularity
  • Hypertrophy & hyperplasia - muscle layer
  • - mucus glands in submucosa
  • - Goblet cell in epithelium
  • inflammatory cells increased
• Airflow reduced increasing resistance - narrowed airways
• IgE tests


  To identify presence of specific allergens
• Use of IgE tests


  • Panel of allergens
• Complications of Asthma


  • Focal atelectasis
  • Emphysema
  • Bronchiectasis
  • Status asthmatics
• Obstructive lung diseases


  Airway diseases that increase resistance to airflow, causing partial or complete obstruction at any level, resulting in reduced FEV1
• Restrictive lung diseases


  Diseases of the lung parenchyma that limit expansion, reducing total lung capacity and expiratory flow rate
• Causes of restrictive lung diseases

  • Chest wall diseases (e.g. severe obesity)
  • Neuromuscular diseases (e.g. poliomyelitis)
  • Pleural diseases
  • Chronic interstitial diseases (e.g. pneumoconiosis, fibrosis)
• Obstructive lung diseases


  • Airflow is reduced due to increased resistance, caused by narrowed airways (e.g. chronic bronchitis, asthma) or reduced outflow pressure (e.g. loss of elastic recoil, emphysema)
• COPD


  Chronic obstructive pulmonary disease involving chronic bronchitis and emphysema, with involvement of bronchi and acini
• Chronic bronchitis


  Persistent productive cough for at least 3 months in at least 2 consecutive years, without identifiable cause, more common in males
• Etiology of chronic bronchitis

  • Smoking (90-95%)
  • Air pollution (sulfur dioxide, nitrogen dioxide, particulate dust, toxic fumes)
  • Industrial pollution (silica, cotton mills, plastic factories, organic and inorganic dusts)
  • Infection
  • Genetic (alpha-1 antitrypsin deficiency, rare)
• Effects of cigarette smoking on chronic bronchitis

  • Destruction, shortening and reduced motility of cilia, inhibition of alveolar macrophage function, hypertrophy and hyperplasia of mucus glands and goblet cells, obstruction of small airways, stimulation of vagus nerve causing bronchoconstriction
• Pathogenesis of chronic bronchitis

  Mucus plugging of airways, infection and pneumonia, obliteration of bronchioles leading to hypoxemia and hypercapnia, air trapping during expiration, smooth muscle hypertrophy, squamous metaplasia
• Morphology of chronic bronchitis

  • Large airways: hyperemic, swollen mucosa, thick wall covered in thick mucus; Microscopy: +/- pus cells with mucus, mucous gland hyperplasia and hypertrophy, increased Reid index (thickness of mucous gland layer to thickness of wall)
• Clinical course of chronic bronchitis


  • Persistent productive cough, muco-purulent sputum if infected, dyspnea on exertion, hypercapnia, hypoxemia and mild cyanosis ("blue bloaters"), cor pulmonale, pulmonary vessel constriction leading to pulmonary hypertension, death from impaired respiratory function and superimposed acute infections