1. Chronic Obstructive Pulmonary Diseases
Chronic Bronchitis
Emphysema
Bronchiectasis
Bronchial Asthma
Small Air way disease Bronchiolitis

2. Pathogenesis
Prolonged exposure to cigarette smoke and/or other air pollutants.
Airway obstruction
at times may result in a check-valve mechanism
leading to overdistension and rupture of alveolar septa, especially if the latter are inflamed and exposed to high positive pressure (i.e. barotrauma).
With loss of alveolar surface in emphysema, there is a decrease in surface tension, resulting in expiratory airway collapse.
Additional investigative work continues in an effort to link disease states to pathogenesis

3. Etiology
By far the most common etiological cause of COPD remains smoking. Even after the client quits smoking, the disease process continues to worsen.
Air pollution
and occupation also play an important role in COPD.
Smog and second-hand smoke contribute to worsening of the disease.

4. Cont.
Occupational exposure to irritating fumes and dusts may aggravate COPD.
Silicosis and other pneumonoconioses may bring about lung fibrosis and focal emphysema.
Exposure to certain vegetable dusts, such as cotton fiber, molds and fungi in grain dust, may increase airway resistance and sometimes produce permanent respiratory impairment.

5. Cont.
Exposures to irritating gases, produce pulmonary edema, bronchiolitis and at times permanent parenchymal damage.
Chlorine
Oxides of nitrogen and sulfur,
Repeated bronchopulmonary infections can also intensify the existing pathological changes, playing a role in destruction of lung parenchyma and the progression of COPD.

6. Chronic Bronchitis
Definition: Chronic bronchitis is a clinical syndrome defined by chronic sputum production
Persistent cough
with sputum production
for at least 3 months
in at least 2 consecutive years
Anatomic site
Bronchus

7. Morphology Hyperemia and edema of mm of lungs
Mucinous secretions or casts filling in the air ways
Increase in the size and numbers of mucous secreting glands
Bronchial or bronciolar mucous plugging, fibrosis, inflammation and fibrosis
Squamous metaplaisa or dysplasia of bronchial epithelium

8. Chronic Bronchitis Pathophysiology
Cilia Damaged
Chronic inflammation
Hypertrophy & hyperplasia of bronchial glands that secrete mucus
Increase number of goblet cells
Cilia are destroyed

9. Chronic Bronchitis Pathophysiology
Narrowing of airway
Starting w/ bronchi  smaller airways
airflow resistance
work of breathing
Hypoventilation & CO2 retention  hypoxemia & hypercapnea

10. Chronic Bronchitis Pathophysiology
Bronchospasm often occurs
End result
Hypoxemia
Hypercapnea
Polycythemia (increase RBCs)
Cyanosis
Cor pulmonale (enlargement of right side of heart

11. Cartilage damage in long standing cases
Degenerative changes, atrophy and loss of bronchial cartilage were common features of most chronic bronchitic specimens
This usually being related to intrinsic changes in the chondrocyte phenotype, including proliferative and matrix-degrading properties.
Mast cells and macrophages were often observed in close association with the bronchial cartilage,
suggesting that inflammatory cells may also contribute to the mechanisms of bronchial cartilage degradation and loss

12. Inflammatory Cells
Studies show that smokers with symptoms of chronic bronchitis have an increased number of inflammatory cells in their bronchial glands when compared with asymptomatic smokers.
This inflammatory process consists predominantly of neutrophils and macrophages, and of an increased proportion of CD8+ T-lymphocytes
Mast cells

13. Mast cells Lymphocytes Neutrophils Macrophages
Macrophages, Mast cells, Lymphocytes and Neutrophils

14. Neutrophils
Lymphocytes
Mast cells
Macrophages

15. This inflammatory process consists predominantly of neutrophils and macrophages, and of an increased proportion of CD8+ T-lymphocytes and
Mast Cells
                              
                              

16. Pathogenesis Chronic irritation of airways
Smoking
Dust
Air pollutants etc
The major risk factor for the development of chronic bronchitis is cigarette smoking
Infective agents Secondary factor
These irritants cause
Hypersecretions of mucous
Subsequent hypertrophy of mucous glands
Metaplasia
inflammation

17. Emphysema
Pulmonary emphysema is described in clinical, radiological and physiologic terms, but the condition is best defined morphologically
Definition:Abnormal enlargement of airspaces distal to the terminal bronchioles with destruction of their wall
It is characterized by destruction and enlargement of alveoli

18. Cont.
Although the normal lung has about 35,000 terminal bronchioles and their total internal cross-sectional area is at least 40 times as great as that of the lobar bronchi but the bronchioles are more delicate and vulnerable.

19. Cont
Bronchioles may be obstructed partially or completely, temporarily or permanently, by thickening of their walls, by collapse due to loss of elasticity of the surrounding parenchyma, or by influx of exudates.

20. Cont
In advanced emphysema, the lungs are large, pale, and relatively bloodless.
They do not readily collapse.
They many contain many superficial blebs or bullae, which occasionally are huge.
The right ventricle of the heart is often enlarged (cor pulmonale), reflecting pulmonary arterial hypertension.

21. Emphysema: Pathophysiology
Structural changes
Hyperinflation of alveoli
Destruction of alveolar & alveolar-capillary walls
Small airways narrow
Lung elasticity decreases

22. Emphysema
Loss of Lung Surface Area for Gas Exchange and Oxygen Transport
Loss of Lung Surface area is due to death of Lung Endothelial Cells
Polycyclic aromatic hydrocarbons (PAHs) in Cigarette Smoke and in Environmental Pollution may cause endothelial cell death

23. Emphysema: Pathophysiology
Mechanisms of structural change
Obstruction of small bronchioles
Proteolytic enzymes destroy alveolar tissue
Elastin & collagen are destroyed
Support structure is destroyed
“paper bag” lungs

24. Emphysema: Pathophysiology
The end result:
Alveoli lose elastic recoil, then distend, & eventually blow out.
Small airways collapse or narrow
Air trapping
Hyperinflation
Decreased surface area for ventilation

25. Emphysema: Clinical Manifestations
Early stages
Dyspnea
Non productive cough
Diaphragm flattens
A-P diameter increases
“Barrel chest”
Hypoxemia may occur
Increased respiratory rate
Respiratory alkalosis
Prolonged expiratory phase
Tripod position

26. Emphysema: Clinical Manifestations
Later stages
Hypercapnea
Purse-lip breathing
Muscle retraction
Use of accessory muscles to breathe
Underweight
No appetite & increase breathing workload
Loss of subcutaneous fat
Lung sounds diminished

27. Clinical Manifestations
Pulmonary function
 residual volume,  lung capacity, DECREASED FEV1, vital capacity maybe normal
Arterial blood gases
Normal in moderate disease
May develop respiratory alkalosis
Later: hypercapnia and respiratory acidosis
Chest x-ray
Flattened diaphragm
hyperinflation

28. Classification Anatomical Distribution Cetriacinar Panacinar
Paraseptal
Irregular

29. Pathogenesis Protease anti Protease Theory Pollutants in environment
Hereditary deficiency of the major protease inhibitors
Laurell and Eriksson –1963 – deficiency of α1-antitrypsin and emphysema
Pollutants in environment
smoking of cigarettes
exhalations from cars, dust from grain
Recruitment of neutrophils
stimulation of macrophages and epithelial cells to produce TNF- α, IL-8 and LTB4
Elastase release from leukocytes and tissue macrophages
Inactivation of α1-antitrypsin by oxidants in tobacco smoke or free radicals released from the neutrophils

31. Diseases in which misfolding of a given protein results in improper trafficking

32. Diseases in which misfolding of a given protein results in improper trafficking
polymers of alpha1 antitrypsin molecules will form. These will be retained in the liver (where alpha1 antitrypsin is produced) and will not reach the lungs

33. increased lung lucency
hyper aeration
increased lung lucency
decreased vessel size
Flattening of the Diaphragm
Increased Lung Height
Decreased Peripheral Vascular Markings

34. Chest X-Ray Changes in Emphysema:
The two primary findings are:
Increased Lung Volumes, i.e., hyperaeration or overinflation.
Lung Destruction (bullae or decreased vascularity which gives increased lung lucency and decreased vessel size ).
In end-stage disease, emphysema and chronic obstructive pulmonary disease can result in pulmonary arterial hypertension and eventually cor pulmonale (cp) - which causes an increase in the pulmonary arterial size, as well as right ventricular enlargement and cardiomegaly.

35. Normal acinus

37. Morphology
Centrilobular Emphysema
Panlobular Emphysema

38. Peripheral alveolar damage
Paraseptal
Peripheral alveolar damage

40. Other types of Emphysema
1 Bullous Emphysema (also known as Bullous Lung Disease): Bullous emphysema is so named when there are multiple large bullae associated with a compromise in pulmonary function. It is usually associated with concomitant emphysema, although occasionally, it can be familial

41. Bullous Emphysema
  Subpleural Type: These subpleural bullae contain only gas with no alveolar remnants or blood vessels. They are often located in the apex of the upper lung zone, and along the costophrenic rim of the middle lobe and lingua, but may be seen in the vicinity of parenchymal scars.
Superficial Type: These bullae are found along the anterior edge of the upper and/or middle lung zones, or lingula, and over the diaphragms. They contains blood vessels and strands of partially-destroyed lung.
Deep Type: These bullae are found within the lung substance and contain strands of partially-destroyed lung tissue and blood vessels.

42. 2.Giant Bullous Emphysema: ("Vanishing Lung Syndrome" or "Primary Bullous Disease of the Lungs")
It is usually associated with young males who show large progressive upper lung zone bullae that are often asymmetric.
The giant bullous lesions occupy greater than or equal to one-third of the hemithorax.

43. Cont.
3.Focal Dust Emphysema ( This is focal emphysema surrounding silicotic nodules.
4.Congenital Lobar Emphysema (CLE) 5.Interstitial Emphysema

44. Bronchiectasis
Bronchiectasis is a chronic lung disease that is characterized by permanent dilatation of the bronchi and fibrosis of the lung.
It is defined as the pathological, irreversible dilation of bronchi , due to destruction of the bronchilal walls and their supporting tissues
It is highly associated with chronic bacterial infection
Often looked at, as the final common pathway of many injurious processes

46. Cont.
Bronchiectasis , although uncommon,bears the potential to cause severe illness , including repeated respiratory infections , disabling cough, purulent sputum, shortness of breath,
chest pain and occasionally hemoptysis, with significant impact on the health and the quality of life of the affected person

47. Types of Bronchiectasis
Bronchiectasis means irreversible dilation and distortion of the bronchi and bronchioles.
Pathologically, bronchiectasis can be divided into four types

51. Cylindrical Bronchiectasis
The first type, cylindrical bronchiectasis, is characterized by uniform dilatation of bronchi, that extends into the lung periphery, without tapering.
Tubular bronchiectasis is simply the absence of normal bronchial tapering and is usually a manifestation of severe chronic bronchitis rather than of true bronchial wall destruction

52. Bronciectasis
Cylindrical Forma

53. Varicose Bronchiectasis
The second type is called varicose bronchiectasis and is characterized by irregular and beaded outline of bronchi, with alternating areas of constriction and dilatation.

54. Saccular Bronchiectasis.
The third type is called cystic or saccular bronchiectasis and is the most severe form of the disease.
The bronchi dilate, forming large cysts, which are usually filled with air and fluid.
Saccular bronchiectasis is the classic advanced form characterized by irregular dilatations and narrowing.
The term cystic is used when the dilatations are especially large and numerous

55. Bronchiectasis
Saccular Form

56. Follicular Bronchiectasis
The fourth type of bronchiectasis is called follicular and is characterized by extensive lymphoid nodules within the bronchial walls.
It usually occurs following childhood infections

57. Cont. Repeated or prolonged episodes of pneumonitis,
Inhaled foreign objects or
Neoplasms have been known to cause bronchiectasis.
When the bronchiectatic process involves most or all of the bronchial tree, whether in one or both lungs, it is believed to be genetic or developmental in origin

58. ASTHMA
Definition
Asthma is a chronic inflammatory disorder of airways.
Many cells and mediators are involved in this process – eosinophils, mast cells and T-lymphocytes.

59. Asthma Reversible inflammation & obstruction Intermittent attacks
Sudden onset
Varies from person to person
Severity can vary from shortness of breath to death

60. Bronchial Hypersensitivity
Chronic inflammation is connected with bronchial hyperreactivity
and leads to episodes of wheezing,
coughing,
tightness in the chest,
breathlessness,
shortage of breath specially at night and in the morning.
This episodes are usually connected with variable obstruction which is reversible spontaneously or by treatment.

61. Types A) Allergic asthma B) Non-allergic asthma
asthma induced by immunological mechanisms.
IgE induced asthma
IgE antibodies triggers early and late-phase of response,
T- lymphocytes late and opožděné responses.
B) Non-allergic asthma
asthma induced by non-immunological triggers Intermittent and persistent

62. Response of Inflammation
Inflammation causes obstruction of airways by:
Acute bronchoconstriction
Swelling of bronchial wall
Chronic production of mucous
Remodeling of airways walls

63. Risk factors: Individual predisposition Environment
genetic variability – 5. a 11. chromosome
atopy,
bronchial hyperreactivity,
male or female,
nation
Environment
exposition to allergens
professional chemicals which lead to sensitivity,
viral and bacterial infection,
food,
smoking,
social and economic society,
number of family members,
psychosomatic influence

64. Asthma: Pathophysiology
Swelling of mucus membranes (edema)
Spasm of smooth muscle in bronchioles
Increased airway resistance
Increased mucus gland secretion

65. Asthma: Pathophysiology
Early phase response: 30 – 60 minutes
Allergen or irritant activates mast cells
Inflammatory mediators are released
histamine, bradykinin, leukotrienes, prostaglandins, platelet-activating- factor, chemotactic factors, cytokines
Intense inflammation occurs
Bronchial smooth muscle constricts
Increased vasodilation and permeability
Epithelial damage
Bronchospasm
Increased mucus secretion
Edema

66. Late phase response: 5 – 6 hours
Characterized by inflammation
Eosinophils and neutrophils infiltrate
Mediators are released mast cells release histamine and additional mediators
Self-perpetuating cycle
Lymphocytes and monocytes invade as well
Future attacks may be worse because of increased airway reactivity that results from late phase response
Individual becomes hyperresponsive to specific allergens and non-specific irritants such as cold air and dust
Specific triggers can be difficult to identify and less stimulation is required to produce a reaction

67. Cells involved in chronic allergic inflammation
1. Eosinophils
2. Mast cells
3. T-lymphocytes
4. Neutrophils
5. Basophils

68. T-lymphocytes
Eosinophils
Basophils
Macrophage
NEUTROPHIL
Mast cell

69. Pathogenesis Acute inflammation Remodeling of airways
Chronic inflammation
Symptoms
of bronchoconstriction
Exacerbation
nonspecific hyperreactivity
Ongoing
obstruction of airway

70. Remodeling
destruction of brush epithelium in airways
swelling of the bronchial wall
stimulation of proliferation of fibroblasts
deposition of collagen in lamina reticularis of basal membrane
hypertrophy of smooth muscles
hyperplasia of goblet cells

71. The process of remodeling is involved by:
Th2 lymphocytes (CD25+, production of IL-4,13,5,6,10)
antigen presenting cells
mast cells (tryptase-converting angiotensin I to angiotensin II,
hypertrophy of smooth muscles, histamin – fibrogenetic effect)
eosinophils (long-living in epithelium and submucoses, create
lipids –PAF, LTC4,LTD4, LTB4, peptides, cytokines, TGF-α,
TGF-β, IL-1,3, GM-CSF, ECP)
alveolar macrophages (production of TNF-α, IL-6)
epithelial cells (desquamation of epithelium, lost of integrity,
TGF-β, IGF-1, KGF- β, alteration of differentiation and
proliferation of epithelial cells, apoptosis)
endothelial cells

72. Cont. myocytes (proliferation of myocytes - after stimulation with IL-
11, which is produced by mezenchymal cells after stimulation
with allergen, PGDF, EGF, the effect of gelatinase A (MMP-2)
and B (MMP-9), production of IL-6,8, eotaxin, PGE2, RANTES,
MCP-1,2,3, expression of ICAM-1, VCAM-1, production of NO,
GM-CSF, IL-5)
fibroblasts (activation of fibroblasts, creation of
myofibroblasts, release of GM-CSF and TGF-β, increasing proinflammatory
activity of eosinophils)

73. Subepithelial structures:
thickness of basal membrane
increasing deposition of extracellular matrix under epithelium
deposition of collagen I., III., IV., V. and VII. in reticular membrane
increasing deposition of proteoglycans (lumican, biblycan,
decorin, fibromodulin, hyaluron, versica)
tenascin (corresponds with activity of chronic inflammation)
fibronectin

74. Decrease of elasticity of the wall Inflammation
Increasing number of mucous glands
Increasing number of smooth muscles fibres
Sever bronchospasms during exacerbation
Increase of mucous secretion during
Release of fibrogenetic factors
Ongoing of inflammatory cells
Elastolysis
Deposition of collagen in basal and Epithelial membranes
Decrease of elasticity of the wall
Inflammation

75. Cytokines involved in pathogenesis of asthma
IL-4
- cross-linking of immunoglobulines in B lymphocytes – production of IgE and
IgG4
- increases of expression of VCAM-1 and mucous secretion
- inhibits of activation of Th1 and production of IFNγ
IL-13
- induces production of IgE a IgG4
- activates mast cells
- increases bronchial hyperreactivity and contractility of smooth muscles, affects
the differentiation of cilia
- induces the production of eotaxin, VCAM-1
- suppress production of pro-inflammatory cytokines

76. Cont.
IL-5
- produced by mast cells and Th2 lymphocytes, epithelial cells and eosinophils
- affects the proliferation and the differentiation of B lymphocytes
- induces expression of IL-2R
- proliferating and differentiating factor for eosinophils
IL-12
- produced by macrophages, dendritic cells and monocytes
- decreases production of Th2 cytokines and then production of IgE and IgG1
- decreases number of eosinophils in peripheral blood and in sputum

77. Cont. IL-10 - large immunosupressive and anti-inflammatory effect
- decreases expression of iNOS, COX2
decreases release of IL-2, expression of MHC class II., CD80, CD86 and
CD32 on the surface of APC and then presentation of allergen, RANTES, IL-5
- correlation with asthma severity

78. Cont. - IFNγ - low levels in atopic people
- stimulatory effects on Th1 cells, inhibitory effects on Th2 cells
- the nebulissation of IFNγ decreases the number of eosinophils in BAL but this effect is not significant
TGF-β
- remodeling
- induction of expression of Fas receptor on the surface of epithelial cells,
activation of apoptosis, phagocytosis by macrophages, exudation of plasma,fibrosis

79. Etiological Classification of asthma:
A. Atopic (allergic) asthma
- in combination with allergic rhinitis, atopic dermatitis, genetic predisposition
- confirmation of spec. IgE antibodies, prick tests, inhalation challenge
B. Endogenous asthma
- without specific known influence, obviously in women after exposition to cold
weather, refract to the standard therapy
C. Exercise induced asthma
- physical exercising, provocation by inhalation of chemicals, cold or hot
weather

80. Cont. D. Aspirin induced asthma
- typical triads-nasal polyps, urticaria and asthma induced by application of
aspirin
- other drugs
E. Allergic bronchopulmonary aspergillosis
- aspergillus acts as an allergen challenge in atopic people and induces
aspergillus asthma or alergic bronchopulmonary aspergillosis
- in the chest radiography are intermitent infiltrates in lungs, the viscosity of
mucous is increased and mucous plugs, bronchiectasia

81. Cont. F. Gastroesophageal reflux - bronchospasm induced by reflex
G. Sinobronchial syndrome
- combination of sinusitis with nasal polyps and with asthma
H. Professional asthma
- induced by inhalation and exposition to industry chemicals
CH. Asthmatic equivalent
- dry cough, irritating, without breathlessness

82. Classification of grading of asthma
Grade 1. Intermitent asthma
- rare symptoms < than 1x per week, short episodes of worsening
- night symptoms 2x monthly
- no symptoms between attacks
- PEF or FEV1 > 80%, variability < 20%
Grade 2. Mild persistent asthma
- symptoms <1x per day >1x per week
- night symptoms > 2x per month
- exacerbation can affect daily activity or sleeping
- PEF or FEV1 > 80%, variability 20-30%

83. Cont. Grade 3. Moderate persistent asthma - Everyday symptoms
- Exacerbation affects daily activity and sleeping
- Night symptoms > 1x per week
- Everyday use of releasing drugs
- PEF or FEV1 between %, variability > 30%
Grade 4. Severe persistent asthma
- Continuous symptoms
- Frequent exacerbation
- Physical activity is decreased
- Frequent night symptoms
- PEF or FEV1 < 60%, variability > 30%

84. Asthma: Early Clinical Manifestations
Expiratory & inspiratory wheezing
Dry or moist non-productive cough
Chest tightness
Dyspnea
Anxious &Agitated
Prolonged expiratory phase
Increased respiratory & heart rate
Decreased PEFR

85. Asthma: Early Clinical Manifestations
Wheezing
Chest tightness
Dyspnea
Cough
Prolonged expiratory phase [1:3 or 1:4]

86. Asthma: Severe Clinical Manifestations
Hypoxia
Confusion
Increased heart rate & blood pressure
Respiratory rate up to 40/minute & pursed lip breathing
Use of accessory muscles
Diaphoresis & pallor
Cyanotic nail beds
Flaring nostrils