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Obstructive Diseases, Bronchiectasis and Drug Injury

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Chronic Bronchitis. Functional disorder with anatomic correlates ' ... Mucus impaction (asthma, chronic bronchitis) Immunodeficiency (IgA, certain IgG) ... – PowerPoint PPT presentation

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Title: Obstructive Diseases, Bronchiectasis and Drug Injury


1
Obstructive Diseases, Bronchiectasis and Drug
Injury
  • Rodney Schmidt MD, PhD
  • HuBio 541

http//courses.washington.edu/hubio541/
2
Obstructive Lung Diseases
3
Obstructive Lung Diseases
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Obliterative Bronchiolotis
  • Idiopathic
  • Concentric endo-luminal scarring of membranous
    bronchioles (lt 1 mm)
  • Post-infectious injury suspected
  • Middle-aged patients
  • Female predilection
  • Progressive
  • Similar lesion seen in lung transplant recipients
    (chronic rejection)

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Obstructive Lung Diseases
9
Obstructive Lung Diseases
10
Obstructive Lung Diseases
11
Bronchial asthma
  • Disorder characterized by
  • Increased irritability, causing
  • Paroxysmal narrowing of bronchioles, resulting in
  • Reversible obstruction
  • Multiple variants with different triggers
  • Unifying theme is abnormal airway sensitivity
    triggering stereotyped response

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Chronic Bronchitis
  • Functional disorder with anatomic correlates
  • Persistent cough with sputum production for at
    least 3 months in two consecutive years
  • Usually due to cigarette smoking but may be
    caused by dusty work environments (industrial
    bronchitis).

15
Morphologic Correlates
  • Submucosal gland hypertrophy
  • Goblet cell metaplasia
  • Mucus plugging of bronchioles
  • Inflammation of bronchioles

16
Submucosal glands
Normal
Chronic bronchitis
17
Chronic bronchitis
Normal
18
Obstructive Lung Diseases
19
Emphysema
  • Defined anatomically
  • Abnormal permanent enlargement of the airspaces
    distal to the terminal bronchiole, accompanied by
    destruction of their walls.
  • i.e., loss of alveolar septa

20
Patterns of Emphysema
Normal
21
Patterns of Emphysema
Normal
Pan-lobular
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Patterns of Emphysema
Normal
Centrilobular
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Normal
Emphysema
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Patterns of Emphysema
Normal
Centrilobular
Pan-lobular
Pan-acinar
Proximal acinar
28
Emphysema
29
Consequences
  • Reduced gas exchange due to loss of alveolar
    septa
  • Fewer capillaries
  • Reduced surface area
  • Airflow obstruction

30
Why Obstructive?
  • Collapse due to loss of septa (Starling resistor)
  • Loss of elastic recoil
  • Elastin in septa
  • Decreased surface tension
  • Associated airway inflammation

Normal
Emphysema
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Bronchiectasis
  • Permanent abnormal dilatation of bronchi and
    bronchioles due to, or associated with, chronic
    necrotizing and scarring inflammation of the
    airways.

34
Bronchiectasis
  • Localized post-obstructive
  • Tumors
  • Foreign bodies
  • Diffuse airway clearance abnormalities
  • Cystic fibrosis
  • Ciliary dysmotility syndromes (e.g. Kartageners)
  • Mucus impaction (asthma, chronic bronchitis)
  • Immunodeficiency (IgA, certain IgG)
  • Post-infectious childhood
  • Measles, influenza, pertussis
  • TB, Staph., mixed organisms

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Drug-Induced Injury
  • Drug reactions are relatively common
  • Any pattern of lung injury is potentially due to
    a drug reaction
  • Diagnosis of a drug reaction is usually clinical
    (NOT involving a biopsy)
  • Most types of drug injury are reversible
  • Prognosis varies with type of injury

38
Criteria for Drug Reaction
  • Prior evidence that drug can be toxic
  • Exposure to drug
  • Sufficient dose
  • Appropriate timing relative to exposure
  • Improvement following drug withdrawal
  • Re-emergence of symptoms during drug challenge
  • Absence of confounding factors (e.g. infection)

39
Types of Drug Reactions
  • Anaphylactic
  • Bronchoconstriction
  • Pleuritis and effusions
  • Edema
  • Acute/evolving injury (cytotoxic)
  • Inflammatory
  • Mononuclear/granulomatous
  • Eosinophilic
  • Vascular disease
  • Airway Disease
  • Fibrosis

40
Drug Reactions Clinical
  • On-Set Drug Exposure
  • Edema Insidious Current
  • Acute/evolving Acute/subacute Delayed
  • Mono.granulomatous Insidious Current
  • Eosinophilic Insidious
    Current
  • Vasculopathy Insidious
    Delayed
  • BOOP Insidious Current
  • OB Insidious Delayed

41
Drug Reactions - Prognosis
  • Edema Reversible
  • Acute/evolving Acute/often fatal
  • Mono.granulomatous Reversible
  • Eosinophilic Reversible
  • Vasculopathy Fixed, may progress
  • BOOP Largely reversible
  • OB Fixed

42
Drug Reactions Therapy
  • Edema Withdrawal
  • Acute/evolving Steroids/withdrawal
  • Mono.granulomatous Steroids/withdrawal
  • Eosinophilic Steroids/withdrawal
  • Vasculopathy None
  • BOOP Steroids
  • OB None
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