Pathophysiology of airway and lung
defensive mechanisms
Prof. Jan Hanacek
Classification of airway and lung defensive
mechanisms
A. Reflexive
B. Non-reflexive
Ad A. - changes of breathing pattern
- cough reflex
- apnoic reflex
- sneezing
- expiration reflex
- aspiration reflex
- larygospasm, bronchospasm
Ad B. Physical defensive mechanisms – air conditioning, aerodynamic filter,
electrostatic filter
Immune mechanisms – cellular and humoral (back to microbiology
and immunology)
Mucociliary clearance – ciliary cinetics, rheology and amount of
mucus, morphology of bronchial mucosa
Airway and lung surface liquid – mucus, surfactant
Protease-antiprotease system – production of proteses and/or
production of antiproteases
Oxidants-antioxidants system – production of oxidants and/or
production of antioxidants
Disturbances of reflexive defensive mechanisms
a) Enormously enhaced
 Causes: - inflammation of airway mucosa,
- inhalation of irritant/toxic gases,
- inhalation of foreign body,
- stimulation of centres regulating breathing, e.g. „cough centre“
 Results: - dissemination of infection in the lung,
-
damage of airway mucosa and rupture of alveolar wall, pneumothorax
fracture of ribs and/or vertebrates
nausea, vomitus, headache
incontinence of urine
chest pain
negative effects on heart function, on circulation, and gas exchange
in lung – „cough syncope“
- disturbances of sleep, food intake
- general exhaustion
Disturbances of reflexive defensive mechanisms
b) Weak or absent (especially cough)
Causes: - functional and/or structural damage of afferent branche,
- central network
- efferents/efectors
e.g. due to brain damage, diabetic neuropathy, inhibition of central
part of defensive mechanisms by drugs
Results: - mucus accumulation with incresed concentration of
infective/toxic factors
- dissemination of infetion/toxins into undamaged lung regions
- disturbances of lung ventilation, distribution of air in the lung
- disturbances of ventilation-perfusion ratio
- hypoxemia  hypoxia, hypercapnia, respiratory failure
Disturbances of non-reflexive defensive mechanisms
Physical defensive mechanisms insufficiency of upper airway:
 Causes: - structural changes of upper airway – inherited, acquired
- chronic inflammation of upper airway
 Results: - chronic inflammation of lower airway
Insuficiency of immune mechanism of airway
 Causes:- insufficiency of cellular defence (due to immune cells abnormalities)
- insufficiency of humoral defence (bacteriostatic lung proteins-e.g.
lysozomes, transferrin, lactoferrin, local immunoglobulins
 Results:- decresed defence of the airway and lung against infections
Disturbances of non-reflexive defensive mechanisms
Disturbances of mucociliary clearance - MCC
Rate of MCC of airway is important to keep the lungs free from toxic , allergic
and infectious materials
 Causes:- inherited cilia disfunction, e.g. Kartagener’s sy.
- acquired disfunction, e.g. due to airway infection (rhino- viruses), toxic
damage by air pollutants (SO2 , NOx , O3 ) cigarette smoke
- changes in amount and rheology of airway mucus
- some drugs (beta-blockers)
These processes lead to reduced or abnormal cilia beating, discontinuity
and/or size of mucus blanket, damage of cilliated cells
 Results:- Congenital Dyskinetic Cilia Syndromes (Immotile Cilia, Ciliary
Dysfunction Sy.,
- Acquired dysfunction of ciliary mechanism
Disturbances of protease-antiprotease system
Tissue proteases: elastase, collagenase, cathepsin G, proteinase 3
Antiprotease system: alpha-1 antitrypsin, antileukoproteinase,
alpha-2-macroglobulin, antichymotrypsin, neutrophil
endopeptidase
Disorder of protease-antiprotease balance
 Causes:
a) Increased production of proteases – e.g. released from Ne, macrophages,
by inflammation, air pollutants
a) Deficiency of antiproteases – iherited or acquired deficiency of
alpha-1-antitrypsin
a) Both of them
 Results: development of lung emphysema
Disorder of oxidant – antioxidant system
Oxidants: superoxid anion, hydrogen peroxid, hydroxyl radical, siglet
molecular oxygen
Antioxidants: supeoxid dismutase, catalase, glutathioperoxidase,
vitamins – C, E, A
trace metals – Se, Zn, Cu Mn
Causes: Incresed production of oxidants
- hyperoxia, inflammation, carcinogenesis, aging, radiation damage
Decreased concentration of antioxidats