THE RESPIRATORY SYSTEM

LUNGS
• Excrete CO2
• Replenish O2
Diseases affecting
• Airways
• Interstitium
• Pulmonary vascular system
 ATELECTASIS
• Loss of lung volume due to inadequate
airspace expansion
Resorption
• Obstruction prevents air from reaching the
distal airways
• Air is absorbed and the lung collapses
– Mucus plug
• Asthma
• Bronchitis
 ATELECTASIS CONT’D
Compression
• Accumulation of fluid in the pleural cavity
– Mechanically collapses the adjacent lung
• Congestive cardiac failure
• Pneumothorax
Microatelectasis
• Non obstructive
• Loss of surfactant
 ATELECTASIS CONT’D
Contraction
• Fibrotic changes hampers expansion
• Increases elastic recoil during expiration
 AIRWAY DISEASE
OBSTRUCTIVE RESTRICTIVE
• Limitation of airflow • Reduced expansion of lung
• Total lung capacity & forced parenchyma
vital capacity (FVC) • FVC is reduced
– normal • Expiratory flow rate normal
– increased
• Decreased expiratory flow
rate
 OBSTRUCTIVE LUNG DISEASE
Asthma
• Episodic, reversible bronchospasm
• Exaggerated bronchoconstrictor response
• Persistent bronchial inflammation
Classification
• Extrinsic
• Intrinsic
 ASTHMA CONT’D
Extrinsic
• Initiated by type 1 hypersensitivity reactions
• Atopic
– Most common
• Serum IgE is 
• Eosinophil count 
• Occupational
• Allergic
 ASTHMA CONT’D
Intrinsic
• Non immune triggering mechanisms
• Affected by stimuli that has no effect on normal
persons
• Serum IgE levels normal
• No personal or family history of allergic
manifestations
Triggers
• Aspirin
• Viral pulmonary infections
• Exercise
 ASTHMA CONT’D
Pathogenesis
• Driven by sensitization of CD4+
• Release cytokines mainly interleukins
– Synthesis of IgE
– Growth of masts cells
• Early (30-60) min
• Late (4-8) hrs
 ASTHMA CONT’D
Early Phase
• Leukotriens C4, D4, E4
– Prolonged bronchoconstriction
• Prostaglandins
– Bronchoconstriction & vasodilatation
• Histamine
– Bronchospasm
– Vascular permeability
• Platelet activating factor
– Aggregation of platelets
• Mast cell tryptase
• Inactivates bronchodilatory peptides
 ASTHMA CONT’D
Late phase
• Reinforcement by
– Basophils
– Neutrophils
– Eosinophils
– Tumor necrosis factor
• Up regulates adhesion molecules
 ASTHMA CONT’D
Clinical Course
• Dyspnea
• Wheezing
• Progressive hyperinflation
• Air trapped distal to the bronchi
Status Asthmaticus
• Acidosis
• Hypoxia
• Death
Treatment
• Bronchodilators
• Corticosteroids
 COPD
• Defined by pulmonary function tests
– Objective evidence of persisting and irreversible
airflow obstruction
• Defined broadly to include
– Chronic bronchitis
– Emphysema
 EMPHYSEMA
Morphologic definition
• Permanent enlargement of the airspaces distal
to the terminal bronchioles accompanied by
destruction of their walls
Types
• Centriacinar
• Panascinar
• Distal acinar
 EMPHYSEMA CONT’D
Centriacinar
• Central or proximal acini affected
• Distal alveoli spared
• Most common in the upper lobes
• Results from cigarette smoking
Panacinar
• Uniform enlargement from respiratory
bronchiole to terminal blind alveoli
• Lower lung zones affected
• Α1 antitrypsin deficiency
 EMPHYSEMA CONT’D
Paraseptal/distal
• Distal acinus affected
• Occurs adjacent to areas of fibrosis, scaring or
atelectasis
• Multiple contiguous enlarged airspaces
– Bullae
 EMPHYSEMA CONT’D
• Present in 50%of persons at autopsy
• More common in men
• Strong association with cigarette smoking
• Disabling in the 5th to 8th decade of life
Pathogenesis
• Arises as a result of 2 imbalances
– Protease anti protease
– Oxidant anti oxidant
 EMPHYSEMA CONT’D
Smokers
• Neutrophils and macrophages accumulate
• Rich in proteases – tissue damage
• Reactive oxygen species inactivates protective anti
proteases
Clinical course – 2 extremes
• Dyspnoea
• Cough
• Wheezing
 EMPHYSEMA CONT’D
• Weight loss
• Barrel chest
• Prolonged expiration
• Sit forward – squeezing air out of lungs
• Pink puffers
Chronic Bronchitis & recurrent infections
• Less prominent dyspnoea
• Retain CO2
– Cyanotic
• Obese
• Blue bloaters
 CHRONIC BRONCHITIS

• Clinical diagnosis
– Persistent productive cough for at least 3
consecutive months in at least 2 consecutive yrs
• Inflammation
• Fibrosis
• Narrowing of the bronchioles
• Co exist with emphysema
 CHRONIC BRONCHITIS
Pathogenesis
• Hypersecretion of mucus
• Hypertrophy of the mucus glands
• Metaplastic formation of mucus secreting
goblet cells
• No Eosinophils
 CHRONIC BRONCHITIS
Clinical course
• Cough
• Hypercapnia
• Hypoxemia
• Cyanosis
Complicated by
• Pulmonary hypertension
• Cardiac failure
 RESTRICTIVE LUNG DISEASES
• Reduced Compliance – more pressure is
needed to expand the lung
Acute
• Abrupt decrement in function with pulmonary
oedma
Chronic
• Insidious development of respiratory
dysfunction
 RESTRICTIVE LUNG DISEASES CONT’D
Direct lung injury Indirect injury
• Pneumonia • Sepsis
• Aspiration • Shock
• Contusion • Drug overdose
• Fat embolism • pancreatitis
• Near drowning
 RESTRICTIVE LUNG DISEASES CONT’D

Clinical Course
• Dyspnoea
• Decreased arterial oxygen pressure
• Bilateral pulmonary infiltrates
• Normal respiratory function returns in 6-12
months
CHRONIC RESTRICTIVE LUNG DISEASE
Interstitial
• Occupational • Immunologic
– Asbestosis – Sarcoidosis
– Silicosis – Rheumatoid Arthritis
• Drug related – Collagen Vascular
diseases
– Bleomycin
– Scleroderma
– Methotrexate
– Busulphan
 VASCULAR LUNG DISEASE
• Pulmonary thromboembolism
– 60-80% silent
– 5% sudden death
– Obstruction
• dypsnoea
• Hemorrhage
• infarction
 PULMONARY INFECTIONS
• Bronchopneumonia
– Patchy distribution of inflammation involving more
than one lobe
• Lobar pneumonia
– Strep pneumoniae responsible for > 90%
– Contiguous airspaces of part or all of the lobe is
filled with exudate
 PNEUMONIAS
Community Acquired Nosocomial
• Strep Gram – ve rods
• Hemophilus • Klebsiella
• Staph aureus • E coli
• Legionella • Pseudomonas
• Klebsiella Aspiration
Clinical Course • Oral flora
• Fever, chills, pleuritic chest Chronic
pain, mucopurulent cough • Nocardia
• Hemoptysis • Actinomyces
 TUBERCULOSIS
• Poverty
• Overcrowding
• Chronic debilitating illness
• Mycobacterium tuberculosis
• Delayed hypersensitivity
– Destructive tissue response
• T cell mediated
 TUBERCULOSIS
Primary Secondary
• Develops in unsensitized • Develops in the sensitized
persons host
• Organism is exogenous • Reactivation decades after
• Hypersensitivity & primary (usual)
increased resistance • Cavitation
• Foci of scaring may harbour Clinical features
bacilli • Malaise, weight loss, fever,
night sweats
 PNEUMOTHORAX
• Air in the pleural sac
• Simple/spontaneous
• Secondary
– Emphysema
– Abscess
– TB
– Cancer
 LUNG TUMORS
• 95% of primary lung tumors arise from the
bronchial epithelium
• 5% miscellaneous group
– Carcinoids
– Bronchial gland tumors
– Mesenchymal malignancies
– Lymphomas
 LUNG TUMORS CONT’D
Bronchogenic Carcinoma
• Relationship with cigarette smoking
• Peak incidence 55-65 yrs
• 2:1 male to female ratio
• 5 yr survival rate of ~14%
 BRONCHOGENIC CARCINOMA -
TYPES

• Histologic types
– Squamous cell
– Adenocarcinoma
– Large cell undifferentiated
– Small cell
 BRONCHOGENIC CARCINOMA -
PATHOGENESIS
Transformation of normal bronchial cells into
malignant cells is unknown – Theories:
• Damage to cellular DNA
• Alteration in cellular oncogene expression
• Tumor derived factors stimulate cellular
division
• Chronic inflammation and areas of scaring
• Genetic factors
 BRONCHOGENIC CARCINOMA -
CLINICAL COURSE
• Silent
• Insidious
• Spread before symptoms are produced
• Develop paraneoplastic syndrome
– Hypercalcemia
– Cushings sndrome
– Clubbing
BRONCHOGENIC CARCINOMA – CLINICAL
COURSE CONT’D
• Chronic cough and expectoration
• Chest pain
• Hoarseness
• Pericardial or pleural effusion
• Atelectasis
Metastasis
 BRONCHOGENIC CARCINOMA -
TREATMENT
• Surgery
– video-assisted thoracoscopy
• Chemotherapy
• Radiotherapy
• Immunotoxins, adjuvant immunotherapy, and
monoclonal antibodies offers major
theoretical promise