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Pathophysiology of Respiratory System

Pathophysiology of Respiratory System

Introduction to Respiratory System

The major function of the lung is to replenish oxygen and excrete carbon dioxide from blood. 10,000 L of air is filtered, moistened, warmed and exchange of Oxygen and Carbon Dioxide take place each day. Lung has full capacity of 6 L but only 500 ml is used by human lung at rest.
Lung Diseases can be classified as:
Upper Respiratory Infection (URI)
o Sinusitis
o Pharyngitis
o Laryngitis
Lower Respiratory Infection (LRI)
o Pneumonia
 Acute
o Aspiration
Chronic
o Chronic Obstructive Pulmonary Disorder (COPD)
Fibrosis
o Smoking
Cancer (common internal disease)

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Pneumonia

Pneumonia is an infection lung (lower respiratory tract – LRI). Pneumonia can be very broadly defined as any infection in the lung.

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Etiology
• The epithelial surfaces of the lung are constantly exposed to many liters of air containing various levels of microbial contaminants; nasopharyngeal flora are regularly aspirated during sleep, even by healthy persons; and other common lung diseases render the lung parenchyma vulnerable to virulent organisms.
• The normal lung parenchyma remains sterile because of the efficiency of a number of immune and non- immune defense mechanisms in the respiratory system, extending from the nasopharynx all the way into the alveolar air spaces.
Defects in innate immunity (including neutrophil and complement defects) and humoral immunodeficiency typically lead to an increased incidence of infections with pyogenic bacteria.

Types

• Bacterial
• Viral
• Fungal
• Other
The clinical presentation may be as
• Acute
• Chronic

Acute bacterial pneumonias can manifest as one of two anatomic and radiographic patterns, referred to as bronchopneumonia and lobar pneumonia.

Bronchopneumonia

Bronchopneumonia implies a patchy distribution of inflammation that generally involves more than one lobe. This pattern results from an initial infection of the bronchi and bronchioles with extension into the adjacent alveoli.

Lobar Pneumonia

The contiguous air spaces of part or all of a lobe are homogeneously filed with an exudate that can be visualized on radiographs as a lobar or segmental consolidation. Streptococcus pneumoniae is responsible for more than 90% of lobar pneumonias. The infection follows a viral upper respiratory tract infection. The onset usually is abrupt, with high fever, shaking chills, pleuritic chest pain, and a productive mucopurulent cough; occasional patients may have hemoptysis.

Complications

It may Spread and cause septicemia, abscess or scarring.

Pathogenesis

Pneumonia involved entire or almost entire lobes and evolved through four stages: congestion, red hepatization, gray hepatization, and resolution. Early antibiotic therapy alters or halts this typical progression.

During the first stage, that of congestion, the affected lobe(s) is (are) heavy, red, and boggy; histologically, vascular congestion can be seen, with proteinaceous fluid, scattered neutrophils, and many bacteria in the alveoli.
Within a few days, the stage of red hepatization ensues, in which the lung lobe has a liver-like consistency; the alveolar spaces are packed with neutrophils, red cells, and fibrin.
In the next stage, gray hepatization, the lung is dry, gray, and firm, because the red cells are lysed, while the fibrinosuppurative exudate persists within the alveoli
Resolution follows in uncomplicated cases, as exudates within the alveoli are enzymatically digested to produce granular, semifluid debris that is resorbed, ingested by macrophages, coughed up, or organized by fibroblasts growing into it

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Tuberculosis

Tuberculosis is a communicable chronic granulomatous disease caused by Mycobacterium tuberculosis. It usually involves the lungs but may affect any organ or tissue in the body. Typically, the centers of tubercular granulomas undergo caseous necrosis.

Primary Tuberculosis

Primary tuberculosis is the form of disease that develops in a previously unexposed and therefore unsensitized patient. Elderly persons and profoundly immunosuppressed patients may lose their sensitivity to the tubercle bacillus, so they may develop primary tuberculosis more than once. About 5% of those newly infected acquire significant disease.
The major consequences of primary tuberculosis are that
• it induces hypersensitivity and increased resistance;
• the foci of scarring may harbor viable bacilli for years,
Secondary Tuberculosis (Reactivation Tuberculosis)
Secondary tuberculosis is the pattern of disease that arises in a previously sensitized host. It may follow shortly after primary tuberculosis, but more commonly it arises from reactivation of dormant primary lesions many decades after initial infection, particularly when host resistance is weakened.

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Asbestosis and Asbestos-Related Diseases

Asbestos is a family of crystalline hydrated silicates with a fibrous geometry.
An increased incidence of asbestos-related cancers in family members of asbestos workers has alerted
the general public to the potential hazards of asbestos in the environment Asbestosis is marked by diffuse pulmonary interstitial fibrosis which make the lung appear as honey comb and may cause pulmonary failure. These changes are indistinguishable from UIP, except for the presence of asbestos bodies, which are seen as golden brown, fusiform or beaded rods with a
translucent center.
The clinical findings in asbestosis are indistinguishable from those of any other chronic interstitial lung disease. Typically, progressively worsening dyspnea appears 10 to 20 years after exposure. The dyspnea is usually accompanied by a cough associated with production of sputum.
The risk of lung carcinoma is increased about five-fold for asbestos workers; the relative risk for mesothelioma, normally a very rare tumor (2 to 17 cases per 1 million persons), is more than 1000 times greater.

Obstructive

In their prototypical forms, the four disorders in this group—emphysema, chronic bronchitis, asthma, and bronchiectasis—have distinct clinical and anatomic characteristics.
Localized: Foreign body, aspiration, tumor
Diffuse – Distal airway diseases
Transient reversible spasm – Asthma
Chronic irreversible permanent – COPD

Emphysema

Emphysema is characterized by abnormal permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls without significant fibrosis.

Types of Emphysema

Emphysema is classified according to its anatomic distribution within the lobule; as described earlier, the acinus is the structure distal to terminal bronchioles, and a cluster of three to five acini is called a lobule.
Dyspnea usually is the first symptom; it begins insidiously but is steadily progressive. In patients with underlying chronic bronchitis or chronic asthmatic bronchitis, cough and wheezing may be the initial complaints. Weight loss is common and may be so severe as to suggest a hidden malignant tumor
Emphysema is a chronic obstructive airway disease characterized by permanent enlargement of air spaces
distal to terminal bronchioles.
Subtypes include centriacinar (most common; smoking related), panacinar (seen in α1-antitrypsin deficiency), distal acinar, and irregular.
Smoking and inhaled pollutants cause ongoing accumulation of inflmmatory cells, releasing elastases and oxidants, which destroy the alveolar walls without adequate mesenchymal repair response.
Most patients with emphysema demonstrate elements of chronic bronchitis concurrently, since cigarette smoking is an underlying risk factor for both; patients with pure emphysema are characterized as “pink puffers.
Pink Puffer:
• Lean/weight loss
• Forward stooping
• Barrel chest
• Flat diaphragm
• Hyperlucent Lung

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Asthma
Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing,
breathlessness, chest tightness, and cough, particularly at night and/or early in the morning. The hallmarks of the disease are intermittent and reversible airway obstruction, chronic bronchial inflmmation with eosinophils, bronchial smooth muscle cell hypertrophy and hyperreactivity, and increased mucus secretion.
Atopic asthma is caused by a TH2 and IgE-mediated immunologic reaction to environmental allergens and is characterized by acute-phase (immediate) and late-phase reactions.
Eosinophils are key inflmmatory cells found in almost all subtypes of asthma; eosinophil products such as major basic protein are responsible for airway damage.
Airway remodeling (sub-basement membrane thickening and hypertrophy of bronchial glands and smooth muscle) adds an irreversible component to the obstructive disease
Chronic hypersensitivity inflammatory disease of bronchi  excess mucous and spasmodic occlusion.
Causes
• Allergic: allergens, infection
• Non-allergic: neurogenic, psychogenic
• Airway

o Hyper responsiveness
o Genetic
• Triggers
o Allergens, Exercise,
o Cold Air, SO2 Particulates
Inducers
o Allergens, Chemical sensitizers, Air pollutants, Virus infections

Signs and Symptoms

• Dyspnoea, wheezing, catching for air.
• Cough – viscous thick sputum
• Tachycardia & chest pain
An attack of asthma is characterized by severe dyspnea with wheezing; the chief diffiulty lies in expiration. The victim labors to get air into the lungs and then cannot get it out, so that there is progressive hyperinflation of the lungs with air trapped distal to the bronchi, which are constricted and filed with mucus and debris. In the usual case, attacks last from 1 to several hours and subside either spontaneously or with therapy, usually bronchodilators and corticosteroids.

Chronic Obstructive Pulmonary Disease

Chronic bronchitis is common among cigarette smokers and urban dwellers in smog-ridden cities; some studies indicate that 20% to 25% of men in the 40- to 65-year-old age group have the disease. The diagnosis of chronic bronchitis is made on clinical grounds: it is defined by the presence of a persistent productive cough for at least 3 consecutive months in at least 2 consecutive years.
In early stages of the disease, the productive cough raises mucoid sputum, but airflow is not obstructed. Some patients with chronic bronchitis may demonstrate hyper responsive airways with intermittent bronchospasm and wheezing. A subset of bronchitis patients, especially heavy smokers, develop chronic outflow obstruction, usually with associated emphysema.
The morphologic basis of airflow obstruction in chronic bronchitis is more peripheral and results from
(1) Small airway disease, induced by goblet cell metaplasia with mucous plugging of the bronchiolar lumen, inflammation, and bronchiolar wall fibrosis, and
(2) Coexistent emphysema
Microbial infection often is present but has a secondary role, chiefly by maintaining the inflammation
and exacerbating symptoms.
Histologic examination demonstrates enlargement of mucus-secreting glands, goblet cell metaplasia, and bronchiolar wall fibrosis.

Clinical Features

In patients with chronic bronchitis, a prominent cough and the production of sputum may persist indefinitely without ventilatory dysfunction. As alluded to earlier, however, some patients develop significant COPD with outflow obstruction. This clinical syndrome is accompanied by hypercapnia, hypoxemia, and (in severe cases) cyanosis (hence the term “blue bloaters”). Differentiation of this
form of COPD from that caused by emphysema can be made in the classic case, but many such patients
have both conditions. With progression, chronic bronchitis is complicated.

Smoking – Pathogenesis

Increase in
o Alveolar marcrophages
o CD8 Lymphocytes
o Neutrophils
o Proteases.
• Tissue irritation / destruction
• Airway damage- Bronchitis
• Alveoli damage- Emphysema.

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Complication of COPD

• Cor Pulmonale – Heart failure.
• Acute Exacerbations.
• Recurrent pneumonia.
• End-stage lung disease.
• Polycythemia – hypoxia.
• Bronchiectasis.
• Lung Cancer

Bronchiectasis

Bronchiectasis is the permanent dilation of bronchi and bronchioles caused by destruction of the muscle and the supporting elastic tissue, resulting from or associated with chronic necrotizing infections. Bronchiectasis is actually a permanent dilatation of bronchi with pus. It is not a primary disease but
rather secondary to persisting infection or obstruction caused by a variety of conditions. Once developed, it gives rise to a characteristic symptom complex dominated by cough and expectoration of copious amounts of purulent sputum. Diagnosis depends on an appropriate history along with radiographic demonstration of bronchial dilation. The conditions that most commonly predispose to
bronchiectasis include:
Lower lobes common
• Complications – Pneumonia, septicemia, meningitis.
• Management – surgical resection

Lung Cancer

Although lungs frequently are the site of metastases from cancers arising in extrathoracic organs, primary lung cancer is also a common disease. Roughly 95% of primary lung tumors are carcinomas Carcinoma of the lung (also known as “lung cancer”) is without doubt the single most important cause of
cancerrelated deaths in industrialized countries.
Smoking-related carcinomas of the lung arise by a stepwise accumulation of a multitude of genetic abnormalities (estimated to be in the thousands for small cell carcinoma) that result in transformation of benign progenitor cells in the luninto neoplastic cells.
• Proportional to duration, amount & quality of smoking & deep inhaling.
• 90% are smokers and 10% are non-smokers
• 20 fold risk if >40cigarettes per day
• >100 fold combined with Asbestos, coal, radon, etc.
• Atypical cells in sputum in 96.7% of smokers – 0.9% in nonsmokers.
• Smoke has several irritants & carcinogens.
o Initiators – Benzo[o]pyrenes
o Promoters – Phenol derivatives
o Radioactive substances – Polonium, C14, K40

Classification

 Benign tumours – rare (Adenoma, Hamartoma)
 Malignant (common):
o Bronchogenic Carcinoma: (95%)
o Bronchial Carcinoid Tumor (5%)
o Other Tumors (<1%)
o Metastasis (common)
 Tumors of Pleura
o Mesothelioma – asbestosis

Types of Bronchogenic Carcinoma

o Small cell carcinoma – SCC – 15-20% (oat cell carcinoma)
o Non-Small cell carcinoma – NSCC– 80%
• Squamous cell carcinoma – 20-30%
• Adeno-carcinoma – 30-40%
• Large cell anaplastic carcinoma

Lung Adenocarcinoma

• It is type of Bronchogenic Carcinoma that occurs peripherally in nonsmokers, usually in females.

Complications

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Local:
o Obstruction
o Effusion
o Pneumonia, lipid, other.
o Bronchiectasis
o Atelectasis
o Haemoptysis
o COPD (risk)
Systemic:
o Cachexia
o Paraneoplastic sy
o Clubbing

o Pulm. Osteoarthropathy.
o Bone pain
o CNS dysfunction

Staging of Lung Cancers

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Mesothelioma

Mesothelioma is Tumor of Pleural covering. Risk factor includes Asbestosis. 50% mortality in first year. Usually poorly diagnosed.

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