Emphysema

Definition 
Emphysema is a pathologic condition of the lung defined as abnormal Emphysema  airspaces

• permanent enlargement of air spaces distal to the terminal bronchioles
• due to destruction of aveolar walls
• and without fibrosis.

Classification.
Although the definition of emphysema describes the basic pathology, this disease can be further divided into four subgroups based on the part of the respiratory acinus (lobule) which is damaged and the location of these damaged lobules within the lung. (Refer to 15-8 and 15-9 in your textbook).

• Centriacinar Emphysema:  
  • Involves primarily the respiratory bronchiole (proximal and central part of the acinus is expanded)
  • The distal acinus or alveoli are unchanged.
  • Occurs more commonly in the upper lobes.
  • Most common type.
  • Seen in cigarette smokers
• Panacinar Emphysema:
  • Involves entire respiratory acinus, from respiratory bronchiole to alveoli  is expanded.
  • Occurs more commonly in the lower lobes, especially basal segments, and anterior margins of the lungs.
  • It is 1/20 as common as centricular emphysema.
  • It is the type seen in alpha 1 - antitrypsin deficiency
• Distal acinar (Paraseptal emphysema):
  • The distal respiratory acinus, including alveolar duct and alveoli, is expanded.
  • Occurs primarily adjacent to the pleura and connective tissue septa, especially in the upper lobes.
  • Extensive involvement of the lung is rare.
  • Some cases of spontaneous pneumothorax may be due to this type of emphysema
• Irregular:( Paracicatritial emphysema)
  • Irregular emphysema is associated with scarring
  • No particular relationship to the acinus .
• Bullous emphysema, by definition, is composed of lesions > 1 cm in diameter, and can be associated with any type of emphysema
• A bleb is a localized pocket of interstitial emphysema, typically subpleural, with no destruction of lung tissue

Pathogenesis

• Emphysema is associated with heavy cigarette smoking. But how does smoke damage the respiratory acinus?
• Protease - antiprotease theory: The walls of acinus are destroyed when there is an imbalance between proteases and anti-proteases in the lung. Protease is an enzyme like elastase, which can digest connective tissue elements. Proteases are found throughout the body, especially in neutrophils and macrophages. To counterbalance the destructive effects of proteases, nature provides inhibitors such as alpha-antitrypsin.
• Smoking increases the level of lung proteases while impairing the action of anti-proteases. Patients with panacinar emphysema may lack alpha-antitrypsin.

Pathophysiology
Progressive dyspnea, over inflated lungs,     barrel chest, hyperresonance, and distant breath sounds.

Chronic bronchitis

Definition

• A patient has chronic bronchitis when he or she has a
  • persistent, productive cough
  • for at least 3 months
  • in at least 2 consecutive years.
• Although chronic bronchitis is defined officially in clinical terms, this condition is a chronic inflammation of the trachea, bronchi and bronchioles which is characterized by hypersecretion of mucous and thickening of the walls of respiratory tree.

Pathology
How are the tubes of the respiratory tree narrowed? The histologic features are

• Chronic inflammation of bronchi (usually lymphocytic)
• Marked increase in the size of the mucus secreting glands of the submucosa in the trachea and large bronchi with excessive mucus secretions in the lumina of the respiratory tree.  The Reid Index is a ratio of the thickness of the gland layer to the thickness of the submucosa. The Reid index measures the gland to wall ratio (normally glands are 1/3 of wall thickness as measured from epithelial basement membrane to cartilage). The ratio is increased in chronic bronchitis.
• Hyperplasia of goblet cells in small bronchi and bronchioles.
• Squamous metaplasia and dysplasia of bronchial epithelium.

Pathogenesis

• Inhaled irritants such as smoking.
• Infections.

Pathophysiology
Persistent, productive cough; dyspnea; expiratory wheezing. Chronic bronchitis:  Clinical picture

Corpulmonale
Central cyanosis
Cyanosis

Mechanics of breathing

Air Flow Profiles in the Airways

1. Cross-Sectional Area of the Airways
   • total cross-sectional area increases exponentially with generation (solid line)
   • forward air flow velocity decreases exponentially with generation (dashed line)
2. Three Types of Air-Flow Profiles
   • continuity equation
     • flow (mL/sec) = vel (cm/sec) * cross-sect area (cm²) * (mL/cm³)
   • Reynold's Number (N_R) = density * mean velocity * diameter / viscosity
   • turbulent flow for N_R > 3000 (gen. 0-6)
   • laminar flow for N_R <2000 (gen. 7-17)
   • diffusive flow with cardiogenic mixing for N_R = 0 (gen. 18-23)

Four Factors Affecting Air-Flow Resistance

1. Airway Caliber
   • laminar flow () = pressure (P) / resistance (R)
   • slope of line = 1/R = conductance
   • resistance (R) to laminar flow 1/radius⁴
   • airway caliber (secretions, bronchoconstriction): < R and < P
2. Air-Flow Profile
   • laminar flow (<) increases linearly with < driving pressure
   • non-laminar flow (<) increases curvilinearly with < driving pressure
   • R_{non-laminar flow} is effectively greater than R_{laminar flow} due to turbulence
   • for any given < P, <_non-laminar <<_laminar
   • or any given <, <P_non-laminar > < P_laminar
3. Airway Generation
   • in general, regional airway resistance decreases as a function of airway generation
   • in specific, the highest regional resistance is at generation 4
     • medium sized bronchi of short length and frequent branchings highly non-laminar air flow with extreme turbulence
4. Lung Volume
   • total airway resistance = summation of serial regional resistances
   • R_total decreases hyperbolically with increases in lung volume
     • conductance_total increases linearly with increases in lung volume (dashed line)
     • increases in lung volume cause increases in radius due to tethering of the airways
   • R_total can be partitioned into two components
     • R_peripheral (gen. 7 - gen. 23): low resistance (laminar & diffusive zones)
     • R_central (nose - gen. 6): high resistance (turbulent flow zone)
     • R_central >>> R_peripheral (50% of resistance in nasal passages alone)

Dynamic Compression of the Airways

1. Flow-Volume Loops
   • air flow (L/sec) is plotted against lung volume (% Vital Capacity)
   • inspiratory and expiratory air flows form a closed loop (clockwise rotation)
   • for any lung volume, max inspiratory air flow is effort dependent
   • for high lung volumes, max expiratory air flow is effort dependent
   • for low lung volumes, max expiratory air flow is effort independent
2. Dynamic Compression of the Airways
   • the expiratory portion of the maximal flow-volume loop has a scooped- out appearance
   • during active, forced expiration P_pleural can actually exceed P_airway
   • this transmural pressure gradient favors airway compression (Starling resistor effect)
   • greater effort ( P_pleural) results in greater compression ( radius) with no change in air flow
   • compression starts at the equal-pressure point (EPP) in the cartilage-free airways within the lung
   • in disease the weakened airways can actually collapse causing air-trapping behind the blockade
   • lip pursing moves the EPP to the mouth, a psychological relief to the patient

Work of Breathing

1. Components of Work
   • elastic work - work to overcome:
     • lung elastic recoil
     • thoracic cage displacement
     • abdominal organ displacement
   • frictional work - work to overcome:
     • air-flow resistance (major)
     • viscous resistance (lobe friction, minor)
   • inertial work - work to overcome:
     • acceleration and deceleration of air (negligible due to low mass of air)
     • acceleration and deceleration of chest wall and lungs (negligible due to overdamping)
2. Graphical Representation of the Major Components of Work
   • work = force * distance pressure * volume / 2
   • elastic work area a-b-c-a
   • inspiratory flow-resistive work area a-i-b-a
   • expiratory flow-resistive work area a-b-e-a
   • negative work area a-e-b-c-a (tone on inspiratory muscles during expiratory air flow)
   • total work W_elastic + W_{inspiratory flow-resistive} + W_negative
   • passive recoil of lungs overcomes the work of expiratory flow-resistance
3. Work of Breathing in Disease
   • restrictive or low compliance diseases (e.g. fibrosis)
     • W_elastic + normal W_{flow-resistive} + W_negative = W_total
   • obstructive or high air flow resistance diseases (e.g. asthma)

     normal W_elastic + W_{flow-resistive} + W_negative = W_total