RESPIRATORY SYSTEM By Dr. Nazar M.T. Jawhar MBChB, HSD, JBPath, EuroBPath Lecturer & consultant pathologist European Board in pathology Jordanian Board in pathology Ph.D university of Jordan
THE LUNG & THE UPPER RESPIRATORY SYSTEM The main function of the lung is to excrete carbon dioxide from the blood & replenish oxygen. The respiratory system includes: The lungs. Upper respiratory tract (nasopharynx, trachea & larynx). Pleural space. The regulatory neural circuits.
The lungs in the chest have a normal pink aerated appearance with minimal anthracotic pigmentation
This is normal lung microscopically. The alveolar walls are thin and delicate. The alveoli are well-aerated and contain only an occasional pulmonary macrophage (type II pneumonocyte)
It is a common approach to organize lung disease into those affecting the airways, interstitium, & the pulmonary vascular system. However, this is an arbitrary classification since a disease in one compartment will affect the others.
Atelectasis (collapse) Definition: It means loss of lung volume due to inadequate expansion of airspaces. Effect of atelectasis: Hypoxemia due to decreased blood oxygenation & shunting of inadequately oxygenated blood from pulmonary arteries into the pulmonary veins. Superimposed infection of the collapsed lung.
Types of atelectasis: Resorption atelectasis: Compression atelectasis (passive atelectasis): Microatelectasis (non-obstructive): Contraction atelectasis:
Resorption atelectasis: Results from airway obstruction. The air already presents gradually become absorbed & alveolar collapse follows. Depending on the level of obstruction, an entire lung, complete lobe, or one segments may be involved.
Examples of obstruction: Intralumenal: thick mucopurulent plug ( most common, as seen postoperatively, in asthmatic patient,& in chronic bronchitis), aspiration of foreign-bodies ( in children) or blood clot ( during oral surgery & during anesthesia). Mural: Tumors especially bronchogenic carcinoma. Compression from out side: as in enlarged lymph node ( as from TB).
Compression atelectasis (passive atelectasis): Due to accumulation of fluid, air, or blood within the pleural space, which mechanically collapses the adjacent lung.
Microatelectasis (non-obstructive): Generalized loss of lung expansion, mostly due to loss of surfactant as in neonatal acute respiratory distress syndrome.
Contraction atelectasis: Due to fibrotic change in the lung which impairs normal expansion.
Atelectasis ( except that caused by contraction) is potentially reversible & should be treated promptly to prevent hypoxemia & infection.
OBSTRUCTIVE LUNG DISEASES: Definition: A group of airway diseases characterized by limitation of airflow and increased resistance due to partial or complete airway obstruction at any level. Types: Include asthma, emphysema, chronic bronchitis, bronchiectasis, cystic fibrosis, and bronchiolitis.
ASTHMA: Characterized by episodic reversible bronchoconstriction resulting from exaggerated response to various stimuli. It is a common disease affecting about 5% of adult population & 7% of children.
Classification: I- Extrinsic asthma: II- Intrinsic asthma:
EXTRINSIC ASTHMA: A common form, develops mostly early in life. - The asthmatic attacks are initiated by type I hypersensitivity reaction induced by exposure to extrinsic antigen.
EXTRINSIC ASTHMA: Three types of extrinsic asthma are recognized: * Atopic Asthma: The commonest type, its onset in the first 2 decades of life, usually associated with other allergic manifestations in the patient & his family. Associated with eosinophilia & high IgE level in the blood. * Occupational asthma. * Allergic bronchopulmonary aspergillosis (bronchial colonization with aspergillus organism).
Mechanism: Involves type I hypersensitivity reaction. ( diagram). Characterized by early phase ( 30-60 minute after the inhalation, caused by primary mediators) & late phase reaction ( develop 4-8 hours after the inhalation, due to secondary mediators).
INTRINSIC ASTHMA:Develops later in life.The triggering mechanisms for bronchospasm are non-immune, and include aspirin, pulmonary viral infection, cold, exercise, psychological stress, inhaled irritants,…No family history is present.The mechanism is not clear, there is no hypersensitivity reaction.
Morphological changes in asthma: The lungs are overinflated. The bronchi and bronchioles are plugged by thick mucus. M.I: - Edema, hyperemia, and inflammatory infiltrate rich in eosinophils is seen in the bronchial wall. - Thickening & hypertrophy of bronchial smooth muscles & submucosal mucus glands. - Thickening of subepithelial basement membrane ( due to the released cytokines stimulate fibrosis).
EMPHYSEMA: It is a chronic obstructive airway disease characterized by permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls. What is the difference between emphysema and overinflation? In overinflation there is no destruction but compensatory overinflation.
Incidence:A common disease that is present in approximately 50% of adults at autopsy ( most of them were asymptomatic).Symptoms mostly manifest after fourth – fifth decades of life and men are more commonly ( and more severely) affected than women.Emphysema either present alone in a pure form or ( commonly) presents with chronic bronchitis.
Etiology:Strong association with heavy cigarette smoking.Deficiency of α1-antitrypsin deficiency.
Pathogenesis: Current evidence indicates that emphysema results from two critical imbalances: - Protease-antiprotease activity. - Oxidant-antioxidant activity.
Proteases: This is a group of proteolytic enzymes that can degrade proteins ( e.g elastase which degrades elastic tissue, proteinsas, cathepsin G). These enzymes are present inside neutrophils and macrophages, they are released during certain conditions as during inflammation.
Antiprotease: In our body, there is another mechanism to counteract the action of these proteases which is the antiprotease mechanism.The most important of which is the α1- antitrypsin, this is a glycoprotein that is synthesized by the liver and is present in the serum and tissue fluids. It is the major inhibitor of proteases and is encoded by a gene present on chromosome 14.
Emphysema is seem to results from the destructive effect of high protease activity in subjects with low antiprotease activity.Who develop emphysema?- Smokers.- Those with hereditary deficiency of α1- antitrypsin.
How smoking predispose to emphysema? Smoking results in accumulation of large no. of neutrophils and macrophges in the alveoli ( especially respiratory bronchioles) possibly because of the direct chemoattractant effect of nicotine as well as the effects of reactive oxygen species contained in the smoke. Smoking also stimulate the release of proteases as elastase and other enzymes from neutrophils and macrophges resulting in destruction in the lung.
Types of emphysema: Two main types according to the anatomic nature: - Centriacinar: - Panacinar:
Centriacinar: Mainly affects the respiratory bronchioles.Most common type.Seen in smokers.Mostly affects the upper lobes.Panacinar:Uniform enlargement of the acini.Seen in patient with α1- antitrypsin deficiency.Mostly in the lower lobes.
Morphology: The lungs appear pale voluminous. Some times with subpleural bullae.
Morphology: Histologically there is thinning and destruction of alveolar septae with enlargement of air-spaces.Clinically: Depends on whether there is pure emphysema ( pink puffer) or associated with chronic bronchitis ( blue bloater). Dyspnea is most important symptom, steadily progressive.
Complications: Respiratory failure with respiratory acidosis. Right sided heart failure ( core pulmonale). Pneumothorax
Conditions related to emphysema: Compensatory emphysema: Compesatory dilation of alveoli in response to loss of lung substance as seen in distention of airspaces in the opposite lung after unilateral pneumonectomy.
Obstructive emphysema: Subtotal obstruction of airways leads to expansion of the distal lung tissue as a result of air trapping.
Interstitial emphysema: Refers to the entrance of air into the connective tissue stroma of the mediastinum or subcutaneous tissue, producing a crackling crepitation. It seen in certain conditions as whooping cough in children and penetrating injuries as fracture rib.
CHRONIC BRONCHITIS: Definition: A type of obstructive airway disease characterized by persistent productive cough with excess mucus secretion for at least 3 consecutive months in at least 2 consecutive years.
Incidence: It is a common condition, affecting approximately 20% of men older than 40 years. It is more common among cigarette smokers & urban dwellers.
Pathogenesis: Inhalation of irritant as cigarette smoke and other air pollutants will induce hypersecretion of the bronchial mucus glands with excessive mucus production. Chronic exposure to cigarette smoke results in damage to bronchioles with resultant inflammation, fibrosis, and narrowing. Squamous metaplasia
Pathogenesis: Coexistent emphysema also contribute to airway obstruction. Superimposed bacterial infection plays a secondary role in exacerbating the symptoms.
Morphology: Marked enlargement and thickening of submucosal mucous glands. The overlying epithelium frequently shows squamous metaplasia which may be followed by dysplastic changes. Variable no. of chronic inflammatory cells are seen in the mucousa.
Complications: Respiratory failure. Rt. Sided cardiac failure ( core pulmonale).
BRONCHIECTASIS Definition: A permanent dilation of bronchi and bronchioles due to destruction of their wall as a result of chronic necrotizing infection.Predisposing factors to bronchiectasis: Bronchial obstruction: Congenital or hereditary conditions: examples: Necrotizing pneumonia:
Bronchial obstruction: Usually results in localized bronchiectasis. Causes of obstruction: Mechanism: Obstruction impairs normal clearing mechanism with subsequent accumulation of secretion, secondary bacterial infection. With time, chronic inflammation leads to damage to bronchial walls with weakening and dilatation.
Congenital or hereditary conditions: examples:Cystic fibrosis: Autosomal recessive condition, characterized by secretion of visid mucus resulting in obstruction and secondary bacterial infection.Immunodeficiency states: due to repeated bacterial infections.Kartagener’s syndrome (immotile cilia syndrome): This is an autosomal recessive disorder characterized by structural abnormalities in the ciliary apparatus resulting in impaired mucociliary clearance of the airway and recurrent infection.
Necrotizing pneumonia: Some times in children measles, whooping cough, and influenza are complicated by the development of suppurative pneumonia which may leads to persistent inflammation in the bronchi and bronchioles ending in destruction and dilatation.
Morphology: Grossly: The condition is either localized to one lobe or is bilateral and mostly affects the lower lobes. We see dilatation of bronchi and bronchioles that can be tracked to the pleura.
M.I: The changes include: Ulceration of the lining epithelium. Infiltration of the bronchi & interstitium by chronic inflammatory cells. The lumen contains inflammatory exudate. Interstitial fibrosis