Respiratory SystemRespiratory System

Anatomy of Respiratory Tract

Trachea

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Principal Bronchi

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Bronchi

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Bronchiole

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Terminal Bronchiole

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Respiratory Bronchiole

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Alveoli

• Acinus is the functional unit of lung whereas alveoli are the chief sites of gaseous exchange.

• Lobule is composed of 3-5 terminal bronchioles with their acini.

• Alveoli are lined by type I pneumocytes (forming 95% of alveolar surface) and type II pneumocytes (responsible for secretion of surfactant and repair of alveoli after type I pneumocyte destruction). The alveoli wall has the presemce of pores of KohnQ for allowing the passage of bacteria and exudate between adjacent alveoli.

• The entire respiratory tract is lined by pseudostratified, tall, columnar ciliated epithelial cells except vocal cords (these have stratified squamous epithelium.

Bronchioles do not have cartilage and submucosal glands in wall like bronchi.

Terminal bronchiole contain maximum smooth muscle relative to the wall thickness.

Broadly, the disease of lung may be divided into obstructive, restrictive, vascular and neoplastic etiologies.

INFECTIVE LUNG DISEASES

1. PNEUMONIA

Infection of the lung parenchyma is called pneumonia. It can be of two types.

Pneumonia

Typical Pneumonia Atypical Pneumonia

Typical Pneumonia Atypical Pneumonia

Infection caused by bacteria most common cause of community acquired pneumonia is streptococcus pneumoniae

And the most common cause of Nosocomial pneumonia is staphylococcus aureus

Infection caused by Mycoplasma, Chlamydia pnemoniae and viruses like RSV Influenza virus, rhinovirus

(most common cause is Mycoplasma pneumoniae.

Characterized by neutrophilic infiltration and presence of intra-alveolar exudates (leading to consolidation).

Characterized by lymphocytic infiltration and presence of alveolar septal and interstitial inflammation with absence of alveolar exudates

Clinical features include onset high grade fever and mucopurulent cough which may also be associated with pleuritic pain.

Clinical features include fever, headache and myalgia. Cough and pleural involvement is uncommon.

• Viral pneumonia result in interstitial infiltrates (therefore called interstitial pneumonia) and may result inn variety of cytopathic effects. E.g. RSV shows bronchiolitis and multinucleate giant cells and CMV and herpes show inclusion bodies.

Furthermore , typical pneumonia can be of two types.

Typical Pneumonia

BronchopneumoniaLobar Pneumonia

LOBAR PNEUMONIA

Consolidation of entire lobe usually caused by streptococcus pneumonia

Following 4 stages of inflammation

1. Congestion: it is due to vasodilation. There is bacteria rich intra-alveolar fluid.

2. Red hepatization: exudate is rich in RBC, neutrophils and fibrin .

3. Gary hepatization: Degradation of RBC and fibrinosuppurative exudates.

4. Resolution: enzymatic degradation of exudate and healing.

Chest X-ray shows opacification of the entire lobe.

Bronchopneumonia

Patch consolidation in the lobe of lungUsually bilateral basal In location due to gravitation of

secretions.Affects extremes of age (Infants or old)Chest X-rays shows patchy opacification of the lobe.

2. Lung Abscess

• Local suppurative process within the lung associated with necrosis of the lung tissue is called lung abscess.

• it is most commonly caused by aspiration of infective material.

• Commonest etiological agent is Staphylococcus aureus.

Causes of Lung abscess

MiscellaneousSepticemboli

PostObstructive

Post pneumonicinfection

Aspiration

Most commonCause

Right lowerLobe is the Most frequentlyAffected

Infection causedBy Staph.aureus, Klebsiella or type 3 pneumococcus

Usually basal, Multiple andDiffusely scattered

Due to primary Or Secondary

DirectHematogenousSpread to lungFrom infectionIn esophagus orPleural cavity

• Clinical feature: fever, productive cough with large amount of sputum, chest pain, weight loss and presence of clubbing of the fingers and toes.

• Characteristic histologic feature:

Suppurative destruction of lung parenchyma within the central area of cavitation. Complication include empyema, brain abscess or meningitis, pulmonary hemorrhage and secondary amyloidosis .

Pulmonary diseases

Obstructive Lung disease Restrictive lung disease

Characterized by increased resistance to airflow due to airway obstruction.

Spirometry reveals FEV1 FVC

Ratio is decreased.

Characterized by decreasedExpansion of the lung

Spirometry reveals reduced total lung capacity

and vital Capacity Q

Example1. Chest wall disorder- Polio,

Obesity; kyphoscoliosis2. Interstitial /infiltrative disease:

Pneumoconiosis, ARDS, Pulmonary fibrosis

3. TUBERCULOSIS(KOCH’S DISEASE)

• Pulmonary tuberculosis is caused by droplet infection (coughing, sneezing etc) due to Mycobacterium tuberculosis.

• It is a strict aerobic bacteria having mycolic acid in its cell wall making it acid fast which means it resists decolourisation by a treatment with a mixture of acid and alcohol.

• The reservoir of infection is a human being with active tuberculosis.

• However, certain clinical condition can increase the risk of tuberculosis like diabetes mellitus, Hodgkin’s lymphoma, chronic lung disease (particularly siliocosis), chronic renal failure, Malnutrition, alcoholism and immunosuppression.

• Infection with M.tuberculosis is different from disease. Infection is the presence of organisms, which may or may not cause clinically significant disease.

• In most of the people, primary tuberculosis is asymptomatic thought it may be associated with fever and pleural effusion.

• Infection with M. tuberculosis typically leads to the development of delayed hypersensitivity to M. tuberculosis antigens, which can be detected by the tuberculin (Mantoux) test.

• A positive tuberculin test result signifies cell-mediated hypersensitivity to tubercular antigens but does not differentiate between infection and diseased.

False- negative Mantoux test

False-positive Mantoux

test

SarcoidosisMalnutrition Hodgkin diseaseImmunosuppression Fulminant tuberculosis

infection by atypical mycobacteriaPrevious vaccination with BCG

Pathogenesis

Macrophages are the primary cells infected by M.tuberculosis. The bacteria enter macrophages by endocytosis.

The bacterial cell wall glycolipid lipoarabinomannan blocks the fusion of the phagosome and lysosome. This is followed by bacterial multiplication inside the macrophages.

• Thus, the initial stages of primary tuberculosis (<3 weeks) in a nonsensitized individual is characterized by bacterial multiplication in the pulmonary alveolar macrophages and airspaces, with resulting bacteremia and spread to multiple sites in the body.

• After about 3 weeks of infection, the TH1 cells are stimulated by mycobacterial antigens and these cells differentiate into mature TH1 cells by the action of

IL-12.

• The mature TH1 cells in the lymph nodes and lungs produce IFN- which stimulates formation of phagolysosome in infected macrophages and causes nitric oxide induced oxidative damage to the cell wall and DNA of the mycobacteria.

• Activated macrophages, stimulated by IFN- , produce TNF and recruit monocytes which then differentiate into the “epithelioid histiocytes”, a characteristic feature of granulomatous inflammation.

• So, immunity to M. tuberculosis is primarily mediated by TH1cells, which stimulate macrophage to kill the bacteria. The immune response is usually accompanied by hypersensitivity and tissue destruction.

• Reactivation of the infection or re-exposure to the bacilli in a previously sensitized host therefore causes activation of defense mechanism and increased tissue necrosis.

Clinical Features

Primary tuberculosis

Develops in a previously unexposed and unsensitized individual. The source of the organism is usually exogenous. The majority of the patient with primary tuberculosis develop latent disease while a minority develops progressive infection.

Primary tuberculosis almost always begins in the lungs. Typically, the inhaled bacilli implant in the distal airspaces of the lower part of the upper lobe or the upper part of the lower lobe due to most of the inspired air being distributed here and form a subpleural lesion.

This subpleural lesion along with the draining lymphatics and the lymph nodes is called as Ghon’s complex. During the first few weeks, there is also lymphatic and hematogenous dissemination to other part of the body.

In majority of the people , development of cell-mediated immunity control the infection. The Gohn’s complex undergoes progressive fibrosis and calcification

(detected radiologically and called as Ranke complex)

• Hisologically, the sites of active disease show a characterized granulomatous inflammatory reaction having the presence of both caseating and non-caseating tubercles.

• There is also presence of Langhans giant cells and lymphocytes immunocompromised people do not form the characterized granulomas.

Secondary tuberculosis :

Secondary tuberculosis is the pattern of disease that arises in a previously sensitized host. It usually result from a reactivation of latent primary lesion after many yrs of an initial infection, particularly when host immunity is decreased or uncommonly may follow primary tuberculosis.

Secondary pulmonary tuberculosis is classically localized to the apex of the upper lobes of the lung (right lung affected more commonly as compared to left) because of high oxygen tension in the apices.

The preexistence of hypersensitivity contributes to an immediate and marked tissue response leading to localization of the infection (the regional lymph nodes are less prominently involved in secondary tuberculosis) and cavitation followed by erosion into an airway (leading to spread of bacilli during coughing).

• Histologically, the active lesion show characteristic tubercles composed of epithelioid cells and Langhans cells with central caseation. The lesion of secondary pulmonary tuberculosis may heal with fibrosis either by itself or after therapy, or it my progress along the following several different pathways.

• Progressive pulmonary tuberculosis is seen in the elderly and the immunosuppressed individuals.

• The apical lesion enlarges with increase in the area of caseation. The erosion of blood vessels (particularly bronchial artery) results in hemoptysis.

• The pleural cavity is associated with pleural effusion or empyema.

• If the treatment is adequate, the disease may be controlled but if it is inadequate, the infection may disseminate through airways, lymphatics or the vascular system.

• Miliary disease occurs when organism drain through lymphatics and blood vessels to the different organs of the body resulting in small yellow- white consolidated lesion. Miliary tuberculosis is most prominent in the liver, bone marrow spleen, adrenal, meninges, kidneys, fallopian, and epididymis.

Note: the most frequent form of extra- pulmonary tuberculosis is lymphadenitis usually in the carvical region and is knows as “ scrofula”. When the vertebrae are affected it is known as pott’s disease.

• The patient present with insidious onset of symptoms like low grade remittent fever usually associated with night sweats, productive cough, weight loss, hemoptysis, dyspnea and pleural effusion.

• The investigations usually reveal lymphocytosis and increased ESR (on hemogram), hilar lymphadenopathy and pleural effusion (on chest X-ray), presence of acid fast bacilli with Ziehl Nielson stainig. The treatment is provided with multiple drugs