Documents
Resources
Learning Center
Upload
Plans & pricing Sign in
Sign Out

Prezentace aplikace PowerPoint

VIEWS: 3 PAGES: 50

									     Pathophysiology of asthma
                 and
chronic obstructive pulmonary disease




                M. Tatár
       OBSTRUCTIVE LUNG DISEASES

   localized: laryngeal constriction, tracheal and bronchial
                  carcinoma, foreign bodies

   generalized: asthma, COPD, bronchiectasis, cystic fibrosis




OBSTRUCTIVE VENTILATORY DISORDER - spirometry


                Airflow limitation
                End of quiet expiration




              0.5
                             -- 0.5
                                2.5
Inspiration
                0        0        0       0   0
                     Inspiration


                              - 2.0
                              + 2.5
  Forced      0.5
expiration
             - 2.0        - 1.5 - 1.0 - 0.5   0
      Forced expiration



                 + 2.0
0.5

+ 2.5         + 2.0 + 1.5 + 1.0   0


              EPP
              ASTHMA - definition

   Chronic inflammatory disorder of the airways

       Mast cells, eosinophils, T-lymphocytes

 Recurrent episodes of wheezing, dyspnoea, and
  cough particularly at night and early morning

Symptoms are associated with airflow limitation that
  is partly reversible either spontaneously or with
                        therapy


Bronchial hyperresponsiveness is present very often
                   Volume

                                    FEV1

             Normal subject


 Asthmatic (after bronchodilator)
Asthmatic (before bronchodilator)




                                       1   2     3     4    5
                                           Time (seconds)
               ASTHMA - classification

A. Intrinsic asthma
• no environmental causes can be identified
• negative skin test to common airborn allergens
• rather negative family history

B. Extrinsic asthma
• atopy, genetic predisposition
•  IgE, mast cells and eosinophils response to allergens

C. Occupational asthma
• sensibilisation of airways to inhalant chemicals
          Development of asthma

               Risk factors
    Predisposing: atopy, gender
    Causal: allergens, aspirin, chemicals
    Contributing: respiratory infections, diet,
             air pollution, smoking


Factors that exacerbate asthma - triggers
      allergens, respiratory infections,
             exercise, emotions
                  Triggers

Respiratory infections
• epithelial damage
• airway inflammation

Exercise  reflex airflow limitation
• cooling of mucosa
• osmolarity changes of fluid lining epithelium

Emotions (laughing, crying, anger, fear)
• hyperventilation
• hypocapnia
Asthma - bronchial hyperresponsiveness



    Instability of the airways =

  exaggerated bronchoconstrictor
response to a wide variety of stimuli



    Key factor - airway inflammation


    Mechanisms: direct and indirect
                   Airway hyperresponsiveness

                        Direct agonists
                       e.g. methacholine




                                                                   Airway with
                                                                   limited airflow
                          Nerve

                                           Mediators
                 SO2, bradykinin




 Indirect agonists                                     Mast cell
e.g. exercise, adenosine, hypotonic
or hypertonic aerosols
antihyperreactiv factors                                prohyperreactiv factors


 2-adrenergic                                              -adrenergic
 VIP/PHM
                                                             cholinergic
 anticholinergic                im balance
                                                             SP/NK
 NEP
                                                             oxygen-free radicals
 antioxidants
   corticoids                                                peptidases




                            Normal airway reactivity
                           Airway hyperresponsiveness
Pathological changes in chronic asthma

     Normal airway                       Airway wall remodeling


                         Epithelium

                     Basement membrane

                       Smooth muscle


                         Mucus plug

                       Mucus glands
          Mechanisms of asthma



      1. Airway inflammation

- recruitments of inflammatory cells from circulation
- endothelial adhesion molecules
- activation of T lymphocytes (Th2 clone)
-  production of IgE, leukotriens, prostanoids
- cytokines (CD4+ Th subtype)


       2. Neural control of airways
                    Neurogenic inflammation

                           Antigen etc.
              Macrophage                  Mast cell

T-lymphocyte                                           Neutrophil

                                   Eosinophil



   Mucus plug                                   Epithelial shedding

Vasodilation                                      Subepithelial fibrosis

                                                       Sensory nerve
Plasma leak
                                                           Efferent nerv
      Oedema
                                     Airway constriction and smooth
                                     muscle hypertrophy/hyperplasia
 Asthma - airflow limitation




1. Acute bronchoconstriction


2. Swelling of the airway wall


3. Chronic mucus plug formation


4. Airway wall remodeling
         Relaxation                         Constriction

                      muscle constriction
                            35 %                       Airway
Normal                                                 narrowing

            R=1                               R = 10



                      muscle constriction              Exaggerated
Asthma                      35 %
                                                         airway
                                                        narrowing
            R=2                               R = 40
                  Risk factors
          (for development of asthma)



               INFLAMMATION



Airway
hyperresponsiveness         Airflow limitation


                                  Symptoms
                Risk factors
            (for exacerbations)
    Asthma is a highly variable disease

Asthma is a chronic inflammatory disease of variable
severity. Worsening and exacerbations of asthma are
associated with episodes of acute inflammation, which
develop on top of persistent underlying chronic
inflammation.

This acute inflammation causes an increase in symptoms
and may also lead to an increased sensitivity to triggers and
a worsening in airway hyperresponsiveness.

The variability and severity of „real life“ asthma is
dependent on a number of factors, including a patient´s
adherence to the prescribed treatment.
           COPD - definition



        Chronic airflow limitation
(  maximum expiratory flow, slow forced
         emptying of the lungs)

 Airflow limitation is slowly progressive
             and irreversible


    Due to varying combinations of:
            • airway disease
             • emphysema
                              COPD


Chronic bronchitis                     Emphysema

• defined in clinical terms      • defined anatomically
• chronic cough with             • permanent, destructive
   sputum production               enlagrement of airspaces
  - (3 months a year,              distal to the terminal
    2 successive years)            bronchioles without
                                   obvious fibrosis
  - excluded cardiac or
   other pulmonary causes
         COPD - risk factors



     Cigarette smoking

 1 - antitrypsin deficiency


 Solid fuel used for indoor heating or
cooking without adequate ventilation

   Heavily polluted environments
         100

                                                       Never smoked

         75


                                 Smoked regularly
FEV1 %




         50                                                  Stopped at
                                                             age 45 yrs

                    Disability
         25                                                  Stopped at
                    Death                                    age 65 yrs

          0
               25                               50            75
                                             Age yrs
    COPD - cellular and biochemical mechanisms


Inflammation: alveolar macrophages, neutrophils


      production of elastase, cathepsine G, collagenase
      oxidative stress in smokers and in COPD patients


    Neutrophil and macrophage enzymes and oxidants
   destroy components of extracellular matrix (collagen,
            elastin, fibronectine, proteoglycans)

        Loss of cellular components of lung parenchyma:
                 - elastase can induce apoptosis
- cells exposed to oxidants may undergo apoptosis or necrosis
COPD - cellular and biochemical mechanisms


                   Imbalance

   proteases              antiproteases system

   oxidants               antioxidants




  Destruction of lung             Small airways
     parenchyma                     disorder
COPD - pathology of peripheral airways



•   mucus plugging
•   goblet cell metaplasia
•   fibrosis
•   smooth muscle hypertrophy
               12




                            Maximal
                6
                        expiratory effort
V´ ( l.s-1 )




                0
                        Spontaneous
                          breath

               -6


                    0   1             2        3       4   5
                               Volume from TLC ( l )
                      100                           IRV
                                                                        IRV

                                                    VT
Lung volume (% TLC)




                                Airflow limit
                      80

                                                                        VT



                      60         Normals




                      40
                            0                    20                           40
                                   Oxygen consumption (ml.min-1.kg-1)
                            Emphysema



                Airway
                narrowing                  Relatively normal
                                           lung region,
Emphysematous                              normal PAO2
region  PAO2



                    V´                     V´
Destruction                                              Relatively
of capillary                   CaO2                    normal CaO2

                       Q´
                                             Q´

Pulm.                                                          Pulm.
artery                                 Normal CaO2             vein
                                       ´
                                   Bronchitis



                Airway narrowing
                                                      Relatively normal
                                                      lung region, normal PAO2
        PAO2



                                                 norm
                       V´                       V´           normal
                                                              CaO2
                                     CaO2
                                                                        CaO2
                     norm Q´                    norm Q´


Pulm. a.                                                               Pulm. v.
                10
PaCO2 ( kPa )




                6




                4
                     0   0,5   1,0   1,5        2,0   2,5   3,0
                                        FEV1 ( l )
                          100



                          80
Oxygen saturation ( % )




                          60



                          40



                          20
                                REM   REM             REM




                                       Sleep period
Components of chronic obstructive pulmonary disease

Emphysema            Emphysema          Chronic bronchitis
but no COPD

                                                    Simple bronchitis




      Asthma                                       Airflow limitation
                                                    by spirometry
               Asthma with no airflow limitation

								
To top