LUNG PATHOLOGY

DR ABOBARIN OLUFUNMILAYO.I

OUTLINE

• INTRODUCTION
• EMBRYOLOGY
• CONGENITAL ANOMALIES
• PULMONARY EDEMA-CARDIOGENIC
• -NON CARDIOGENIC
• -EDEMA OF UNDETERMINED ORIGIN.
• ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME.
• OBSTRUCIVE AND RESTRICTIVE LUNG DISEASES.
• PULMONARY INFECTIONS- COMMUNITY ACQUIRED ACUTE PNEUMONIAS
• COMMUNITY ACQUIRED ATYPICAL PNEUMONIAS .
• HOSPITAL ACQUIRED PNEUMONIAS
• ASPIRATION PNEUMONIAS
• LUNG ABSCESS.
• CHRONIC PNEUMONIAS.

OUTLINE

• PNEUMONIAS IN THE IMMUNOCOMPROMISED
• PULMONARY DISEASE IN THE HIV.
• LUNG TRANSPLANTATION.
• TUMOURS
• PNEUMOTHORAX
• PLEURA

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EMBRYOLOGY

• Occurs in five stages. Initial development includes development of lung bud from distal end of respiratory diverticulum during week 4.

CONGENITAL ANOMALIES OF THE LUNG

• Pulmonary hypoplasia
• Foregut cysts
• Pulmonary sequestration
• tracheal and bronchial anomalies atresia, stenosis, tracheoesophageal fistula
• vascular anomalies,
• congenital pulmonary airway malformation,
• congenital lobar overinflation (emphysema).

CONGENITAL ANOMALIES OF THE LUNG

• Pulmonary hypoplasia is a defect in the development of both lungs (one may be more affected than the other) that results in decreased lung size. It is caused by abnormalities that compress the lung or impede lung expansion in utero, such as congenital diaphragmatic hernia(usually left sided) oligohydramnios, bilateral renal agenesis (Potter sequence).
• Foregut cysts arise from abnormal detachments of primitive foregut and are most often located in the hilum or middle mediastinum. Foregut cysts are classified as bronchogenic (most common), esophageal, or enteric depending on its lining epithelium. A bronchogenic cyst is rarely connected to the tracheobronchial tree. It is lined by ciliated pseudostratified columnar epithelium .Its wall contains bronchial glands, cartilage, and smooth muscle. They may be incidental findings or symptoms may occur due to compression or infection.

ATELECTASIS(lung collapse)

• Pulmonary sequestration is a discrete area of lung tissue that:
• (1) is not connected to the airways and
• (2) has an abnormal blood supply arising from the aorta or its branches.
• Extralobar sequestration is external to the lung and most commonly presents in infants as a mass lesion. It may be associated with other congenital anomalies. Intralobar sequestration occurs within the lung. It usually presents in older children, often due to recurrent localized infections or bronchiectasis.

ATELECTASIS(lung collapse)

• Atelectasis refers either to:
• 1) incomplete expansion of the lungs (neonatal atelectasis) or to
• 2) the collapse of previously inflated lung, and results in areas of poorly aerated pulmonary parenchyma.
• It s a reversible disorder (except in cases of fibrosis).When significant, atelectasis can predispose to infection and reduce oxygenation.
• The main types of acquired atelectasis, which is encountered principally in adults, are the following :

ATELECTASIS(lung collapse)

• RESORPTION ATELELCTASIS:stems from obstruction of an airway. Over time, air is resorbed from distal alveoli, which collapse. Since lung volume is diminished, the mediastinum shifts toward the atelectatic lung. Airway obstruction is most often caused by excessive secretions (e.g., mucus plugs) or exudates within smaller bronchi, as may occur in bronchial asthma, chronic bronchitis, bronchiectasis, and postoperative states. Aspiration of foreign bodies and intrabronchial tumors may also lead to airway obstruction and atelectasis.
• COMPRESSION ATELECTASIS: results whenever significant volumes of fluid (transudate, exudate, or blood), tumor, or air (pneumothorax) accumulate within the pleural cavity. With compression atelectasis, the mediastinum shifts away from the affected lung.
• CONTRACTION ATELECTASIS:occurs when focal or generalized pulmonary or pleural fibrosis prevents full lung expansion

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PULMONARY EDEMA

• Pulmonary edema (excessive interstitial fluid in the alveoli) can result from hemodynamic disturbances (cardiogenic pulmonary edema) or increased capillary permeability due to microvascular injury (non-cardiogenic pulmonary edema).
• Causes of pulmonary edema are varied but can be widely classified as
• Hemodynamic
• Non-hemodynamic
• Edema of undetermined origin

Hemodynamic Pulmonary Edema

• hemodynamic pulmonary edema results from increased hydrostatic pressure most commonly in a setting of left sided congestive heart failure.
• GROSS FEATURES
• Edema accumulates initially in the basal regions of the lower lobes because hydrostatic pressure is greatest in these sites (dependent edema).
• HISTOLOGY
• EARLY:the alveolar capillaries are engorged, and there is an intra-alveolar transudate that appears as finely granular pale pink material. Alveolar microhemorrhages and hemosiderin-laden macrophages (“heart failure” cells) may be present. transudative
• LATER :as seen in long standing mitral stenosis, hemosiderin-laden macrophages are abundant, and fibrosis and thickening of the alveolar walls cause the soggy lungs to become firm and brown (brown induration). These changes not only impair respiratory function but also predispose to infection.

Non cardiogenic Pulmonary edema

• Non-cardiogenic pulmonary edema is caused by injury of the alveolar septa. Primary injury to the vascular endothelium or damage to alveolar epithelial cells (with secondary microvascular injury) produces an inflammatory exudate that leaks into the interstitial space and, in more severe cases, into the alveoli.
• Injury-related alveolar edema is an important feature of a serious and often fatal condition, acute respiratory distress syndrome

ACUTE LUNG INJURY

• Acute lung injury (ALI) is characterized by the abrupt onset of hypoxemia and bilateral pulmonary edema in the absence of cardiac failure (non-cardiogenic pulmonary edema). Acute respiratory distress syndrome (ARDS) is a manifestation of severe ALI.
• Both ARDS and ALI are associated with
• 1) inflammation-associated increases in pulmonary vascular permeability,
• edema, and
• epithelial cell death.

ACUTE LUNG INJURY

• ALI is a complication of diverse conditions including both pulmonary and systemic disorders In many cases, several predisposing conditions are present (e.g., shock, oxygen therapy, and sepsis).
• ACUTE INTERSTITIAL PNUEMONIA
• It is an uncommon type of ALI which appears acutely in the absence of known triggers and follows a rapidly progressive clinical course.

PATHOGENESIS.

• Endothelial activation by inflammatory mediators (eg TNF)produced by nearby alveolar macrophages secondary to pneumocyte injury.In severe injury endothelial activation may be by circulating inflammatory mediators.
• Adhesion and extravasation of neutrophils. Neutrophils adhere to the activated endothelium and migrate into the interstitium and the alveoli, where they degranulate and release inflammatory mediators including proteases, reactive oxygen species, and cytokines.
• Accumulation of intra-alveolar fluid and formation of hyaline membranes.

PATHOGENESIS.

• Resolution of injury: as the inflammatory stimulus lessens, macrophages remove intra-alveolar debris and release fibrogenic cytokines such as transforming growth factor β (TGF-β) and platelet-derived growth factor.
• These factors stimulate fibroblast growth and collagen deposition, leading to fibrosis of alveolar walls.
• Residual type II pneumocytes proliferate to replace type I pneumocytes, reconstituting the alveolar lining. Endothelial restoration occurs through proliferation of uninjured capillary.
• The lesions in ARDS are not evenly distributed, and as a result there are typically areas that are stiff and poorly aerated and regions that have nearly normal levels of compliance and ventilation. There is thus ventilation –perfusion mismatch that worsens the hypoxemia and cyanosis

MORPHOLOGY

In the acute exudative stage, the lungs are heavy, firm, red, and boggy. They exhibit congestion, interstitial and intra-alveolar edema, inflammation, fibrin deposition, and diffuse alveolar damage. The alveolar walls become lined with waxy hyaline membranes that are morphologically similar to those seen in hyaline membrane disease of neonates.

OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASES

• Obstructive lung diseases are characterized by an increase in resistance to airflow due to diffuse airway disease, which may affect any level of the respiratory tract. Common obstructive lung diseases include chronic obstructive pulmonary disease, asthma, and bronchiectasis.
• Restrictive diseases are characterized by reduced expansion of lung parenchyma and decreased total lung capacity. They occur in two broad kinds of conditions:
• (1) chest wall disorders (e.g., severe obesity, pleural diseases, kyphoscoliosis, and neuromuscular diseases such as poliomyelitis) and
• (2) chronic interstitial and infiltrative diseases, such as pneumoconioses and interstitial fibrosis.
• Diagnosis of any of these two diseases is based primarily on pulmonary function tests.

OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASES

• In obstructive lung diseases, pulmonary function tests show decreased maximal airflow rates during forced expiration, usually expressed as forced expiratory volume at 1 second (FEV1) over forced ventilatory capacity (FVC).
• An FEV1/FVC ratio of less than 0.7 generally indicates obstructive disease. Expiratory airflow obstruction may be caused by a variety of conditions,each with characteristic pathologic changes and different mechanisms of airflow obstruction.

OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASES

• restrictive diseases are associated with proportionate decreases in both total lung capacity and FEV1, such that the FEV1/FVC ratio remains normal.

OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASES

OBSTRUCTIVE LUNG DISEASES

• These include :

I)chronic obstructive pulmonary disease (COPD) which manifests as

a)chronic bronchitis

b)emphysema

II) asthma

III)bronchiectasis

While asthma is distinguished from chronic bronchitis and emphysema by the presence of reversible bronchospasm, some patients with otherwise typical asthma also develop an irreversible component

Conversely, some patients with otherwise typical COPD have a reversible component. Clinicians commonly label such patients as having COPD/asthma

OBSTRUCTIVE LUNG DISEASES

OBSTRUCTIVE LUNG DISEASES

OBSTRUCTIVE LUNG DISEASES

• COPD IS a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities caused by exposure to noxious particles or gases.
• RISK FACTORS

1) There is a strong association between heavy cigarette smoking and COPD. Women and African Americans who smoke heavily are more susceptible than other groups.

2)poor lung development early in life,

3)exposure to environmental and occupational pollutants,

4)airway hyperresponsiveness,

5)genetic polymorphisms. Recognizing that emphysema and chronic bronchitis o

EMPHYSEMA

• Emphysema is defined by irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls. Subtle but functionally important small airway fibrosis (distinct from chronic bronchitis) is also present and is a significant contributor to airflow obstruction. Emphysema is classified according to its anatomic distribution within the lobule. involved, emphysema is subdivided into four major types:
• (1) centriacinar,
• (2) panacinar,
• (3) paraseptal,

(4) irregular.

Of these, only the first two cause clinically significant airflow obstruction

EMPHYSEMA

• Centriacinar (centrilobular) emphysema. Centriacinar emphysema is the most common form, constitutes over 95% of clinically significant cases. It occurs predominantly in heavy smokers with COPD. the central or proximal parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared.
• Panacinar (panlobular) emphysema: associated with α1-antitrypsin deficiency and is exacerbated by smoking.
• the acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli. In contrast to centriacinar emphysema, panacinar emphysema tends to occur more commonly in the lower zones and in the anterior margins of the lung, and it is usually most severe at the bases.

EMPHYSEMA

• Distal acinar (paraseptal) emphysema. underlies many cases of spontaneous pneumothorax in young adults. In this type the proximal portion of the acinus is normal, and the distal part is predominantly involved. The emphysema is more striking adjacent to the pleura, along the lobular connective tissue septa, and at the margins of the lobules. . It occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lungs. The characteristic finding is multiple enlarged airspaces, ranging from less than 0.5 cm to more than 2.0 cm.

EMPHYSEMA

PATHOGENESIS OF EMPHYSEMA

1)Toxic injury and inflammation.

2)Protease-antiprotease imbalance charcterised by chronic deficiency of protective antiproteases,this has a genetic basis in patients with deficiency of the protease antiprotease alpha -1- antitrypsin deficiency

3)Oxidative stress.

4)Infection

Generally, in patients with smoking-related disease, the upper two-thirds of the lungs are more severely affected. Large alveoli can easily be seen on the cut surface of fixed lungs Apical blebs or bullae may appear in patients with advanced disease.

Microscopically, abnormally large alveoli are separated by thin septa with focal centriacinar fibrosis.

CHRONIC BRONCHITIS

• Chronic bronchitis is defined clinically as persistent cough with sputum production for at least 3 months in at least 2 consecutive years in the absence of any other identifiable cause.
• Pathogenesis
• Mucus hypersecretion
• Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. smoking leads to acquired CFTR dysfunction, which in turn causes the secretion of abnormal, dehydrated mucus that exacerbates the severity of chronic bronchitis.
• Inflammation
• Infection.

COPD

ASTHMA

• Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation and variable expiratory airflow obstruction that produces symptoms such as wheezing, shortness of breath, chest tightness, and cough, which vary over time and in intensity.
• TYPES

Atopic Asthma. This type of asthma is a classic example of an IgE-mediated (type I) hypersensitivity reaction. The disease usually begins in childhood and is triggered by environmental allergens, such as dusts, pollens, cockroach or animal dander, and foods, which most frequently act in synergy with other proinflammatory environmental cofactors, most notably respiratory viral infections. A positive family history of asthma is common, and a skin test with the offending antigen in these patients results in an immediate wheal-and-flare

ASTHMA

• Non-Atopic Asthma. Patients do not have evidence of allergen sensitization, and skin test results are usually negative. A positive family history of asthma is less common in these patients. Respiratory infections due to viruses (e.g., rhinovirus, parainfluenza virus, and respiratory syncytial virus) are common triggers in non-atopic asthma. Inhaled air pollutants such as tobacco smoke, sulfur dioxide, ozone, and nitrogen dioxide may also contribute to the chronic airway inflammation and hyperreactivity in some cases. in some instances attacks may be triggered by seemingly innocuous events, such as exposure to cold and even exercise.

ASTHMA

• Drug-Induced Asthma. Several pharmacologic agents provoke asthma. Aspirin-sensitive asthma is an uncommon type, occurring in individuals with recurrent rhinitis and nasal polyps. These individuals are exquisitely sensitive to small doses of aspirin as well as other non-steroidal antiinflammatory medications, and they experience not only asthmatic attacks but also urticaria. Aspirin and related drugs trigger asthma in these patients by inhibiting the cyclooxygenase pathway of arachidonic acid metabolism, leading to a rapid decrease in prostaglandin E2. Normally prostaglandin E2 inhibits enzymes that generate proinflammatory mediators such as leukotrienes B4, C4, D4, and E4, which are believed to have central roles in aspirin-induced asthma.
• Occupational Asthma. This form of asthma may be triggered by fumes (epoxy resins, plastics), organic and chemical dusts (wood, cotton, platinum), gases (toluene), or other chemicals (formaldehyde, penicillin products). Only minute quantities of chemicals are required to induce the attack, which usually occurs after repeated exposure. The

ASTHMA

ASTHMA

• A characteristic finding in sputum or bronchoalveolar lavage specimens of patients with atopic asthma is Curschmann spirals, which may result from extrusion of mucus plugs from subepithelial mucous gland ducts or bronchioles. Also present are numerous eosinophils and Charcot-Leyden crystals composed of the eosinophil-derived protein galectin-10. The other characteristic histologic findings of asthma, collectively called airway remodeling include:
• • Thickening of airway wall
• • Sub–basement membrane fibrosis (due to deposition of type I and III collagens) • Increased vascularity
• • Increase in the size of the submucosal glands and number of airway goblet cells • Hypertrophy and/or hyperplasia of the bronchial wall muscle with increased extracellular matrix While acute airflow obstruction is primarily attributed to muscular bronchoconstriction, acute edema, and mucus plugging, airway remodeling may contribute to chronic irreversible airway obstruction

BRONCHIECTASIS

• Bronchiectasis is a disorder in which destruction of smooth muscle and elastic tissue by inflammation stemming from persistent or severe infections leads to permanent dilation of bronchi and bronchioles. Its now uncommon due to proper treatment but may develop due to:

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•A)Congenital or hereditary conditions that predispose to chronic infections, including

cystic fibrosis,

intralobar sequestration of the lung,

immunodeficiency states,

primary ciliary dyskinesia,

Kartagener syndrome

BRONCHIECTASIS

• B) Severe necrotizing pneumonia caused by bacteria, viruses, or fungi; this may be a single severe episode or recurrent episodes.
• C)Bronchial obstruction, due to tumor, foreign body, or mucus impaction; in each instance the bronchiectasis is localized to the obstructed lung segment.
• D) Immune disorders, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and the post-transplant setting (chronic rejection after lung transplant and chronic graft-versus-host disease after hematopoietic stem cell transplantation).
• E)Idiopathic

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RESTICTIVE LUNG DISEASES

• Restrictive lung disorders fall into two general categories:
• (1) chronic interstitial and infiltrative diseases, such as pneumoconioses and interstitial fibrosis of unknown etiology,
• (2) chest wall disorders (e.g., neuromuscular diseases such as poliomyelitis, severe obesity, pleural diseases, and kyphoscoliosis), which are not discussed here.
• Chronic interstitial pulmonary diseases are a heterogeneous group of disorders characterized predominantly by inflammation and fibrosis of the lung interstitium associated with pulmonary function studies indicative of restrictive lung disease.

IN GENERAL……

• Diffuse restrictive diseases are categorized based on histology and clinical features into fibrosing, granulomatous ,eosinophilic /smoking related diseases and other types.
• Many of the entities are of unknown cause and pathogenesis, and some have an intra-alveolar as well as an interstitial component.
• Patients present with:
• dyspnea,
• tachypnea,
• end-inspiratory crackles,
• cyanosis, without wheezing or other evidence of airway obstruction.

IN GENERAL

• The classic functional abnormalities are reductions
• in diffusion capacity,
• lung volume, and
• lung compliance.
• Chest radiographs show bilateral lesions that take the form of small nodules, irregular lines, or ground-glass shadows, all corresponding to areas of interstitial fibrosis.
• Although the entities can often be distinguished in their early stages, advanced forms are hard to differentiate because all result in diffuse scarring of the lung, often referred to as end-stage lung or honeycomb lung. Eventually, secondary pulmonary hypertension and rightsided heart failure (cor pulmonale) may result.

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IDIOPATHIC PULMONARY FIBROSIS

• Idiopathic Pulmonary Fibrosis Idiopathic pulmonary fibrosis (IPF) refers to a clinicopathologic syndrome marked by progressive interstitial pulmonary fibrosis and respiratory failure.
• Cause of IPF remains unknown but its notewothy that IPF usually occurs in genetically predisposed individuals who are prone to abberant repair of recurrent alveolar epithelial injuries caused by environmental exposures. This repair occurs under the influence of fibrogenic cytokines such as TGF-β.

PNEUMOCONIOSIS

A non-neoplastic lung reaction or disease resulting from inhalation of mineral dusts, chemical fumes and vapours encountered in the workplace.Factors influencing development of pnuemoconiosis include:

1)Dust retention:influenced by a) the dust concentration in ambient air,

b)duration of exposure c)effectiveness of clearance mechanisms. cigarette smoking, that impairs mucociliary clearance significantly increases the accumulation of dust in the lungs.

2)Particle size. Particles 1-5μm can reach as far as the small terminal airways and airsacs and are said to be the most dangerous

PNEUMOCONIOSIS

• 3) Particle solubility and cytotoxicity.
• 4)inflammation
• 5)Tobacco smoking

COAL WORKERS PNEUMOCONIOSIS

• Coal workers’ pneumoconiosis is lung disease caused by inhalation of coal particles and other admixed forms of dust. Dust reduction measures in coal mines around the globe have drastically reduced its incidence. The spectrum of lung findings in coal workers is wide, varying from: asymptomatic anthracosis,
• simple coal workers’ pneumoconiosis
• complicated coal workers’ pneumoconiosis,
• progressive massive fibrosis, in which lung function is compromised.

MORPHOLOGY

• Carbon deposits are dark black in color and are readily visible grossly and microscopically.
• Anthracosis is the most innocuous coal-induced pulmonary lesion in coal miners and is also seen to some degree in urban dwellers and tobacco smokers.
• Simple coal workers’ pneumoconiosis is characterized by coal macules (1 to 2 mm in diameter) and somewhat larger coal nodules. Coal macules consist of carbon-laden macrophages.
• Coal nodules also contain a delicate network of collagen fibers.
• Although these lesions are scattered throughout the lung, the upper lobes and upper zones of the lower lobes are more heavily involved.
• Complicated coal workers’ pneumoconiosis (progressive massive fibrosis) occurs on a background of simple disease and generally requires many years to develop.

RESTRICTIVE LUNG DISEASES-GRANULOMATOUS DISEASES

• SARCOIDOSIS
• Sarcoidosis is a systemic granulomatous disease of unknown cause that may involve many tissues and organs. It usually occurs in adults younger than 40 years of age but can affect any age group. The prevalence is higher in women especially African –american women. It is rare among the Chinese and Southeast Asians

PATHOGENESIS

• though several lines of evidence suggest that sarcoidosis is a disease of disordered immune regulation in genetically predisposed individuals, its etiology is unknown. There are several immunologic abnormalities in the local milieu of sarcoid granulomas that suggest a cell-mediated immune response to an unidentified antigen.

PRESENTATION

• Most patients present with insidious onset of respiratory abnormalities (shortness of breath, cough, chest pain, hemoptysis) or of constitutional signs and symptoms (fever, fatigue, weight loss, anorexia, night sweats).

SARCOIDOSIS-MORPHOLOGY

• . Virtually every organ in the body has been described as being affected by sarcoidosis. Involved tissues contain well-formed non-necrotizing or non caseating granulomas composed of aggregates of tightly clustered epithelioid macrophages, often with giant cells. Central necrosis is unusual.
• Laminated concretions composed of calcium and proteins known as Schaumann bodies and stellate inclusions known as asteroid bodies are found within giant cells

ASTEROID BODIES

Asteroid Bodies: Asteroid bodies may be seen in the cytoplasm of epithelioid or giant cells in sarcoidosis as eosinophilic, stellate or spider-like inclusions. The radiating filamentous arms contain complex lipoproteins, calcium, phosphorus, silicon, and aluminum. Asteroid bodies are not specific for sarcoidosis and can be seen in numerous other lymphadenopathies such as silicone lymphadenopathy

SARCOIDOSIS-MORPHOLOGY

• The lung is a common site of involvement. Macroscopically, there is usually no demonstrable alteration.
• in advanced cases coalescence of granulomas produces small nodules that are palpable or visible as 1 to 2 cm, noncaseating, noncavitated consolidations.
• Lymph nodes-granulomas especially mediastinal and hilar lymph nodes
• Spleen-granulomas
• Liver-granulomas around the portal triads.
• Skin,eye( iritis,iridocyclitis),lacrimal glands ,salivary glands involvement are also common.

PULMONARY EMBOLISM

• Blood clots that occlude the large pulmonary arteries are almost always embolic in origin. The usual source—thrombi in the deep veins of the leg.
• Pulmonary embolism usually occurs in patients with a predisposing condition that produces an increased tendency to clot (thrombophilia). Patients often have cardiac disease or cancer or have been immobilized for several days or weeks prior to the appearance of a symptomatic embolism. Patients with hip fractures are at particularly high risk.
• Hypercoagulable states, either primary (e.g., factor V Leiden, prothrombin mutations, and antiphospholipid syndrome) or secondary (e.g., obesity, recent surgery, cancer, oral contraceptive use, pregnancy), are important risk factors.
• Indwelling central venous lines can be a nidus for formation of right atrial thrombi, which can embolize to the lung

PULMONARY EMBOLISM

• The pathophysiologic response of pulmonary embolism depend on a)the extent to which pulmonary artery blood flow is obstructed,
• b)the size of the occluded vessels, the number of emboli,
• C) the cardiovascular health of the patient.
• Emboli have two deleterious pathophysiologic consequences:
• 1)respiratory compromise due to the nonperfused, although ventilated, segment.
• 2)hemodynamic compromise due to increased resistance to pulmonary blood flow caused by the embolic obstruction.
• Sudden death often ensues, largely as a result of the blockage of blood flow through the lungs. Death may also be caused by acute right-sided heart failure (acute cor pulmonale).

PULMONARY HYPERTENSION

• Pulmonary hypertension is defined as a mean pulmonary artery pressure greater than or equal to 25 mm Hg at rest. Based on underlying mechanisms, the WHO has classified pulmonary hypertension into five groups:
• (1) pulmonary arterial hypertension, a diverse collection of disorders that all primarily impact small pulmonary muscular arteries;
• (2) pulmonary hypertension due to left heart failure;
• (3) pulmonary hypertension due to lung diseases and/or hypoxia;
• (4) chronic thromboembolic pulmonary hypertension and other obstructions
• (5) pulmonary hypertension with unclear and/or multifactorial mechanisms.

CAUSES OF PULMONARY HYPERTENSION

• . It is most frequently associated with structural cardiopulmonary conditions that increase either pulmonary blood flow, pulmonary vascular resistance, or left heart resistance to blood flow. Some of the more common causes are the following:

• Chronic obstructive or interstitial lung diseases (group 3). These diseases obliterate alveolar capillaries, increasing pulmonary resistance to blood flow and, secondarily, pulmonary blood pressure.

• Antecedent congenital or acquired heart disease (group 2). Mitral stenosis, for example, causes an increase in left atrial pressure and pulmonary venous pressure that is eventually transmitted to the arterial side of the pulmonary vasculature, leading to hypertension.

• Recurrent thromboemboli (group 4). Recurrent pulmonary emboli may cause pulmonary hypertension by reducing the functional cross-sectional area of the pulmonary vascular bed, which in turn leads to an increase in pulmonary vascular resistance.

• Autoimmune diseases (group 1). Several of these diseases (most notably systemic sclerosis) involve the pulmonary vasculature and/or the interstitium, leading to increased vascular resistance and pulmonary hypertension.

PNEUMONIAS

• Pneumonia can be defined as any infection of the lung parenchyma.
• They generally from a breakdown of local defense mechanisms or when the systemic resistance of the host is impaired.
• Examples of breakdown of these local defenses are :

1)Loss or suppression of the cough reflex due to

Coma

Anaesthesia

Neuromuscular disorders

Drugs

Chest pain

PNEUMONIAS

• 2)injury to the mucociliary apparatus-cigarette smoke, viral diseases, genetic defects in ciliary function.
• 3)accumulation of secretions in cystic fibrosis and bronchial obstruction.
• 4)interference with phagocytic or bactericidal action of alveolar macrophages by alcohol, tobacco smoke, anoxia or oxygen intoxication.
• 5)pulmonary congestion and oedema.

• Defects in innate immunity –neutrophil and complement defects.
• Defects in adaptive immunity-
• A)Humoral immunodeficiency lead to increased incidence of infections with pyogenic bacteria.
• B) Cell mediated immune deficiency lead to increased infections with intracellular microbes such as mycobacteria and herpes viruses, pneumocystic jiroveci.

CLASSIFICATION OF PNEUMONIAS

• Pnuemonias can be classified by:
• A)aetiologic agent
• B)clinical setting in which the infection occurs.

COMMUNITY ACQUIRED PNEUMONIA

• May be bacterial or viral.
• Bacterial invasion makes the lung parenchyma causes the lung to be filled with an inflammatory exudate thus causing consolidation.
• Predisposing factors include:

1)Extremes of age.

2)Chronic diseases(COPD, Congestive heart failure , DM).

3)Congenital or acquired immune deficiency.

4)Decreased or absent splenic functions.

• Factors which determine the precise form of pneumonia include;

aetiologic agent,

host reaction,

the extent of involvement.

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COMMUNITY ACQUIRED BACTERIAL PNEUMONIA

• Streptococcus pneumoniae, or pneumococcus, is the most common cause of community-acquired acute pneumonia. . The presence of numerous neutrophils containing the typical gram-positive, lancet-shaped diplococci supports the diagnosis of pneumococcal pneumonia, but it must be remembered that S. pneumoniae is a part of the endogenous flora in 20% of adults, and therefore false-positive results may be obtained.
• H. influenzae pneumonia, is a pediatric emergency and has a high mortality rate,it may follow a viral respiratory infection. There are encapsulated and nonencapsulated forms. There are six serotypes of the encapsulated form (types a to f), of which type b is the most virulent. Routine use of vaccines to protect against the encapsulated forms has reduced its incidence. However the incidence of the non virulent ,non encapsulated forms of H. influenza is presently increasing .

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COMMUNITY ACQUIRED BACTERIAL PNEUMONIA

• Moraxella catarrhalis is recognized as a cause of bacterial pneumonia, especially in the elderly. It is the second most common bacterial cause of acute exacerbation of COPD.
• Staphylococcus aureus is an important cause of secondary bacterial pneumonia in children and healthy adults following viral respiratory illnesses (e.g., measles in children and influenza in both children and adults). Staphylococcal pneumonia is associated with a high incidence of complications, such as lung abscess and empyema. Intravenous drug users are at high risk for development of staphylococcal pneumonia in association with endocarditis. It is also an important cause of hospital-acquired pneumonia.

COMMUNITY ACQUIRED BACTERIAL PNEUMONIA

• Klebsiella pneumoniae is the most frequent cause of gramnegative bacterial pneumonia. It commonly afflicts debilitated and malnourished people, particularly chronic alcoholics.
• Pseudomonas aeruginosa causes pneumonia in cystic fibrosis and immunocompromised patients. It is common in patients who are neutropenic, and it has a propensity to invade blood vessels with consequent extrapulmonary spread. Pseudomonas most commonly causes hospital acquired infections.
• Mycoplasma pneumonia are particularly common among children and young adults. They occur sporadically or as local epidemics in closed communities (schools, military camps, and prisons).

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CLINICAL FEATURES OF BACTERIAL PNEUMONIA

• The major symptoms of community-acquired acute bacterial pneumonia are abrupt onset of high fever, shaking chills, and cough producing mucopurulent sputum and occasionally hemoptysis. When pleuritis is present it is accompanied by pleuritic pain and pleural friction rub. The whole lobe is radiopaque in lobar pneumonia, whereas there are focal opacities in bronchopneumonia

CLINICAL FEATURES OF BACTERIAL PNEUMONIA

• Bacterial pneumonia has two patterns of anatomic distribution: lobular bronchopneumonia and lobar pneumonia .
• Patchy consolidation of the lung is the dominant characteristic of bronchopneumonia while consolidation of a large portion of a lobe or of an entire lobe defines lobar pneumonia.
• These anatomic categorizations may be difficult to apply in individual cases because patterns overlap. The patchy involvement may become confluent, producing lobar consolidation. Moreover, the same organisms may produce either pattern depending on patient susceptibility.

GROSS

• In lobar pneumonia, four stages of the inflammatory response have classically been described:
• congestion,
• red hepatization,
• gray hepatization,
• And resolution.
• Congestion, the lung is heavy, boggy, and red. It is characterized by vascular engorgement, intra-alveolar edema fluid containing a few neutrophils, and the presence of bacteria, which may be numerous.
• Red hepatization, there is massive confluent exudation, as neutrophils, red cells, and fibrin fill the alveolar spaces .On gross examination, the lobe is red, firm, and airless, with a liver-like consistency, hence the name hepatization.
• HEPATIZATION is conversion into a substance resembling the liver, a state of the lungs when engorged with effuse matter so that they are no longer pervious to the air.

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GROSS

• Gray hepatization is marked by progressive disintegration of red cells and the persistence of a fibrinosuppurative exudate resulting in a color change to grayish-brown.
• In the final stage of resolution, the exudate within the alveolar spaces is broken down by enzymatic digestion to produce granular, semifluid debris that is resorbed, ingested by macrophages, expectorated, or organized by fibroblasts growing into it.

GROSS

• Bronchopneumonia is characterised by consolidated areas of acute suppurative inflammation. The consolidation may be confined to one lobe but is more often multilobar and frequently bilateral and basal because of the tendency of secretions to gravitate to the lower lobes. Well-developed lesions are slightly elevated, dry granular, gray-red to yellow, and poorly delimited at their margins.

Histology

the reaction usually elicits a neutrophil-rich exudate that fills the bronchi, bronchioles, and adjacent alveolar spaces .

Complications of pneumonia include:

(1) tissue destruction and necrosis, causing abscess formation (particularly common with pneumococcal or Klebsiella infections).

(2) spread of infection.

PNEUMONIA COMPLICATIONS

• Complications of Bacterial pneumonia
• Abscess formation
• Empyema
• Bacterial dissemination to the heart valves,
• pericardium,
• brain,
• kidneys,
• joints metastatic abscesses,

. (A) Acute pneumonia. The congested septal capillaries and numerous intra-alveolar neutrophils are characteristic of early red hepatization. Fibrin nets have not yet formed

(B) Early organization of intra-alveolar exudate, seen focally to be streaming through the pores of Kohn (arrow).

(C) Advanced organizing pneumonia. The exudates have been converted to fibromyxoid masses rich in macrophages and fibroblasts.

COMMUNITY ACQUIRED VIRAL PNUEMONIA

• Generally viruses implicated in the causation of community acquired pneumonia produce disease through similar general mechanisms, these include:�Tropisms that allow them to attach to and enter respiratory lining cells.
• Viral replication and gene expression : this leads to cytopathic changes, inducing cell death and secondary inflammation.
• The resulting damage and impairment of local pulmonary defenses, such as mucociliary clearance, may predispose to bacterial superinfections, which are often more serious than the viral infection itself.

COMMUNITY ACQUIRED VIRAL PNUEMONIA

• Common viral infections include:
• influenza virus types A and B,
• respiratory syncytial viruses,
• human metapneumovirus,
• adenovirus,
• rhinoviruses,
• rubeola, and
• varicella viruses.

CLINICAL FEATURES

• Manifests as upper respiratory tract infection or chest colds
• Fever
• Headache
• Myalgia
• Cough may be absent.
• Ventilation-perfusion mismatch due to edema and exudation

MORPHOLOGY OF VIRAL COMMUNITY ACQUIRED PNEUMONIA

• Similar morphologic changes can be seen.
• Upper respiratory infection is characterised by mucosal hyperemia and swelling,
• infiltration of the submucosa by mononuclear cells (mainly lymphocytes and monocytes),
• overproduction of mucus secretions.
• The swollen mucosa and viscous exudate may plug the nasal channels, sinuses, or the Eustachian tubes, leading to suppurative secondary bacterial infection.
• Virus-induced tonsillitis causing hyperplasia of the lymphoid tissue within the Waldeyer ring is frequent in children

MORPHOLOGY OF VIRAL COMMUNITY ACQUIRED PNEUMONIA

• Lung involvement may be quite patchy or may involve whole lobes bilaterally or unilaterally.
• . Predominant is an interstitial inflammatory reaction involving the walls of the alveoli.
• Superimposed bacterial infection modifies this picture by causing ulcerative bronchitis, bronchiolitis, and bacterial pneumonia.
• Some viruses, such as herpes simplex, varicella, and adenovirus, may be associated with necrosis of bronchial and alveolar epithelium and acute inflammation.

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HEALTH CARE ASSOCIATED PNEUMONIA

• Health care–associated pneumonia was recently described as a distinct clinical entity associated with several risk factors. These are hospitalization of at least 2 days within the recent past;
• presentation from a nursing home or long-term care facility; attending a hospital or hemodialysis clinic.
• recent intravenous antibiotic therapy,
• chemotherapy,
• wound care.

methicillin-resistant S. aureus and P. aeruginosa are the most commonly isolated organisms.

These patients have a higher mortality than those with community-acquired pneumonia.

HOSPITAL ACQUIRED PNEUMONIA

• pulmonary infections acquired in the course of a hospital stay. common in patients with severe underlying disease, immunosuppression,
• prolonged antibiotic therapy, or

invasive access devices such as intravascular catheters.

Patients on mechanical ventilation (high risk).

Hospital acquired pneumonia are serious and often life-threatening because they are superimposed on underlying diseases.

S. aureus, Enterobacteriaceae and Pseudomonas species are the most common isolates. The same organisms predominate in ventilator-associated pneumonia, with gram negative bacilli being somewhat more common in this setting

ASPIRATION PNEUMONIA

• Aspiration pneumonia occurs in markedly debilitated patients or those who aspirate gastric contents either while unconscious (e.g., after a stroke) or during repeated vomiting.
• These patients have abnormal gag and swallowing reflexes that predispose to aspiration.
• The resultant pneumonia is partly chemical due to the irritating effects of gastric acid and partly bacterial (from the oral flora).
• Typically, more than one organism is recovered on culture, aerobes being more common than anaerobes.
• This type of pneumonia is often necrotizing, pursues a fulminant clinical course, and is a frequent cause of death.
• lung abscess is a common complication

LUNG ABSCESS

• The term pulmonary abscess describes a local suppurative process that produces necrosis of lung tissue.

May be due to oropharyngeal surgical or dental procedures, sinobronchial infections or bronchiectasis.

Usually due to mixed infections because of the inhalation of foreign material. These microbial agents include anaerobic organisms normally found in the oral cavity, including members of the Bacteroides, Fusobacterium, and Peptococcus genera. These causative organisms are introduced by the following mechanisms:

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LUNG ABSCESS

A)Aspiration of infective material (commonest)

• Risk factors include
• suppressed cough reflexes (e.g., acute alcohol intoxication, opioid abuse, coma, anesthesia, seizure disorders),
• severe dysphagia (e.g., neurologic deficits, esophageal disease), protracted vomiting,
• poor dental hygiene.
• Aspiration first causes pneumonia, which progresses to tissue necrosis and formation of lung abscess.

LUNG ABSCESS

B)Previous lung infection. Postpneumonic abscess formations are usually associated with S. aureus, K. pneumoniae, and pneumococcus. Posttransplant or otherwise immunosuppressed individuals are at special risk.

C)Septic embolism. Infected emboli may arise from thrombophlebitis in any portion of the systemic venous circulation or from the vegetations of infective bacterial endocarditis on the right side of the heart and lodge in the lung.

D) Neoplasia. Secondary infection is particularly common in bronchopulmonary segments obstructed by a primary or secondary malignancy in the lung (postobstructive pneumonia).

• Miscellaneous. Traumatic penetrations of the lungs; direct extension of suppurative infections from the esophagus, spine, subphrenic space, or pleural cavity; and hematogenous seeding of the lung by pyogenic organisms all may lead to lung abscess formation

CLINICAL FEATURES OF LUNG ABSCESS

Patients with pulmonary abscesses present like those with bronchiectasis and characteristically include:

cough

fever

copious amounts of foul-smelling purulent or sanguineous sputum.

Chest pain

weight loss are common.

Clubbing of the fingers and toes may appear.

The diagnosis can be only suspected from the clinical findings and must be confirmed radiologically.

Whenever an abscess is discovered in older individuals, it is important to rule out an underlying carcinoma, which is present in 10% to 15% of cases.

CLINICAL FEATURES OF LUNG ABSCESS

• The course of abscesses is variable. With antimicrobial therapy, most resolve, leaving behind a scar. Complications include extension of the infection into the pleural cavity, hemorrhage, the development of brain abscesses or meningitis from septic emboli, and (rarely) secondary amyloidosis

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MORPHOLOGY

• Abscesses vary from a few millimeters to large cavities of 5 to 6 cm They may affect any part of the lung and may be single or multiple.
• The cardinal histologic change in all abscesses is suppurative destruction of the lung parenchyma within the central area of cavitation.

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• Pulmonary abscesses due to aspiration are more common on the right (because of the more vertical right main bronchus) and are most often single.
• Abscesses that develop in the course of pneumonia or bronchiectasis are usually multiple, basal, and diffusely scattered.
• Septic emboli and pyemic abscesses are multiple and may affect any region of the lungs.

CHRONIC PNEUMONIAS

• Chronic pneumonias are typically granulomatous reactions caused by bacteria e.g., Mycobacterium tuberculosis or fungi e.g. Histoplasma capsulatum

Blastomyces dermatitidis.

Coccidioides immitis

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HISTOPLASMOSIS

• H. capsulatum infection is acquired by inhalation of dust particles from soil contaminated with bird or bat droppings that contain small spores (microconidia).
• It is endemic along the Ohio and Mississippi rivers , Caribbean, Mexico, Central and South America, parts of eastern and southern Europe, Africa, eastern Asia, and Australia.
• Like M. tuberculosis, H. capsulatum is an intracellular pathogen that is found mainly in phagocytes. The clinical presentations and morphologic lesions of histoplasmosis bear a striking resemblance to those of tuberculosis, including :

HISTOPLASMOSIS

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• (1) a self-limited and often latent primary pulmonary involvement
• (2) chronic, progressive, secondary lung disease, which is localized to the lung apices and causes cough, fever, and night sweats;
• (3) spread to extrapulmonary sites, including mediastinum, adrenal glands, liver, or meninges;
• (4) widely disseminated disease in immunocompromised patients.
• Histoplasmosis can occur in immunocompetent individuals but is more severe in those with depressed cell mediated immunity

identification of the 3- to 5-µm thin-walled yeast forms, which may persist in tissues for years.

BLASTOMYCOSIS

• Blastomyces dermatitidis is a soil-inhabiting dimorphic fungus, common around central and southeastern United States, Canada, Mexico, the Middle East, Africa, and India. There are three clinical forms: pulmonary blastomycosis,
• disseminated blastomycosis,
• cutaneous form.

Blastomyces is a round, 5- to 15-µm yeast cell that divides by broad-based budding. It has a thick, double-contoured cell wall, and visible nuclei (Fig. 15.38). Involvement of the skin and larynx is associated with marked epithelial hyperplasia, which may be mistaken for squamous cell carcinoma

COCCIDIOIDOMYCOSIS

• Common around southwestern and western united states and also mexico.
• Approximately 10% of infected people develop lung lesions, and less than 1% of people develop disseminated Coccidiomyces immitis infection, which frequently involves the skin and meninges.
• Within macrophages or giant cells, C. immitis is present as thickwalled, nonbudding spherules 20 to 60 µm in diameter, often filled with small endospores. A pyogenic reaction is superimposed when the spherules rupture to release the endospores
• Rare progressive C. immitis disease involves the lungs, meninges, skin, bones, adrenals, lymph nodes, spleen, or liver. At all these sites, the inflammatory response may be purely granulomatous, pyogenic, or mixed

PNEUMONIA IN THE IMMUNOCOMPROMISED HOST

• Patients whose immune defenses are suppressed by disease, immunosuppressive therapy for organ or hematopoietic stem cell transplants, chemotherapy for tumors, or irradiation are not only susceptible to pneumonia from the usual pathogens but also pneumonias by opportunistic infections.
• Usually more than one opportunistic agent is involved and the mortality rate is high.

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• The appearance of a pulmonary infiltrate, with or without signs of infection (e.g., fever), is one of the most common and serious complications. The infiltrates can be local or diffuse
• Of these, the ones that commonly involve the lung can be classified according to the etiologic agent: (1) bacteria (P. aeruginosa, Mycobacterium species, L. pneumophila, and Listeria monocytogenes), (2) viruses (cytomegalovirus [CMV] and herpesvirus), and (3) fungi (P. jiroveci, Candida species, Aspergillus species, the Phycomycetes,Cryptococcus neoformans

PULMONARY DISEASE IN THE HIV INFECTED PERSONS

• The use of potent antiretroviral agents and effective chemoprophylaxis has markedly altered the incidence and outcome of pulmonary disease in HIV-infected persons, the wide range of infectious agents and other pulmonary lesions make diagnosis and treatment a distinct challenge.
• Therefore the diagnostic work-up of these patients may be more extensive (and expensive) than would be necessary in an immune competent individual.
• Another reason is the fact that even common pathogens may present with atypical manifestations.
• Bacterial lower respiratory tract infections caused by the “usual” pathogens are among the most serious pulmonary disorders in HIV infection,even though such individuals are at risk of the opportunistic organisms.These agents includee S. pneumoniae, S. aureus, H. influenzae, and gram-negative rods.The pneumonias by these organisms in HIVinfected persons are more common, more severe, and more often associated with bacteremia than in those without HIV infection.

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PULMONARY DISEASE IN THE HIV INFECTED PERSONS

• The CD4+ T-cell count determines the risk of infection with specific organisms:
• bacterial and tubercular infections are more likely at higher CD4+ counts (>200 cells/mm3 ).
• Pneumocystis pneumonia usually strikes at CD4+ counts less than 200 cells/mm3 .
• CMV, fungal, and Mycobacterium avium-intracellulare complex infections are uncommon until the disease is very advanced (CD4+ counts less than 50 cells/mm3 ).
• Pulmonary infiltrates in HIV-infected individuals are infectious in etiology. A host of noninfectious diseases, including Kaposi sarcoma nonHodgkin lymphoma and lung cancer, occur with increased frequency and must be excluded.

LUNG TRANSPLANTATION

• The most common indications are end-stage COPD, idiopathic pulmonary fibrosis, cystic fibrosis, and idiopathic/familial pulmonary arterial hypertension. These are non neoplastic terminal lung diseases.
• Bilateral lung transplantation offers better survival as compared to single lung, the latter may be performed to benefit two recipients from a single (and all too scarce) donor. When bilateral chronic infection is present (e.g., cystic fibrosis, bronchiectasis), both lungs of the recipient must be replaced to remove the reservoir of infection. With improving surgical and organ preservation

LUNG TRANSPLANTATION

.The transplanted lung is subject to two major complications:

infection and rejection. •

infections in lung transplant patients are essentially those of any immunocompromised host, discussed earlier.

early posttransplant period (the first few weeks), bacterial infections are most common.

CMV pneumonia occurs less frequently and is less severe due to ganciclovir prophylaxis and matching of donor and recipient CMV status.

P. jiroveci pneumonia is rare, since almost all patients receive adequate prophylaxis, usually with trimethoprim-sulfamethoxazole (Bactrim).

Fungal infections are mostly due to Aspergillus and Candida species, and they may involve the bronchial anastomotic site and/or the lung.

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LUNG TRANSPLANTATION

Acute lung allograft rejection occurs to some degree in all patients despite routine immunosuppression. It most often appears several weeks to months after surgery but also may present years later or whenever immunosuppression is decreased. Patients present with fever, dyspnea, cough, and radiologic infiltrates. Since these are similar to the picture of infections, diagnosis often relies on transbronchial biopsy.

• Chronic lung allograft rejection is a significant problem in at least half of all patients by 3 to 5 years posttransplant. It is manifested by cough, dyspnea, and an irreversible decrease in lung function due to pulmonary fibrosis

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LUNG TUMOURS

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• LUNG CANCER
• INTRODUCTION:
• Lung cancers are the most frequently diagnosed major cancers in the world and the most common cause of cancer deaths worldwide.

It is commoner among the males than females however, incidence of lung cancer has been decreasing among the males compared to the females dues to decreased smoking rates among the men.

AETIOLOGY;

Largely due to stepwise accummulation of genetic abnormalties mostly from cigarette smoking.

Theres has been substantial evidence linking lung cancer to tobacco smoking as 80% of lung cancer patients are patients who are currently smoking or just stopped smoking. Frequency of lung cancer is closely linked to

the amount of daily smoking

the tendency to inhale

duration of smoking.

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LUNG CANCER

• Important factors worthy of note in tobacco smoking are
• Only 11% of heavy smokers (smoke more than 40cigaretres per day for several years)develop lung cancer in their life time.
• Women are more susceptible to tobacco carcinogens than men.
• Studies have shown association between cigarette smoking and carcinoma of the mouth, pharynx, larynx, esophagus, pancreas, cervix, kidney and the bladder.
• Cigar and pipe smoking increase the risk of lung cancer than cigarette smoking.
• Second hand smoke is also linked to lung cancer

LUNG CANCER

• Industrial hazards:
• Industrial exposure to asbestos, chromium, arsenic, uranium ,nickel, mustard gas and high dose ionising radiation increase the risk of developing lung cancer. The risk is higher if such industrial workers are smokers.
• Air pollution.
• Chronic exposure to air pollutants such as Radon may cause lung irritation, inflammation and repair. These set the stage for carcinogenesis. The risk is higher in smokers and second hand smokers.

LUNG CANCER

• Genetics: stepwise acummulation of oncogenic driver mutations eventually result in cells exhibiting all the hallmarks of cancers.
• Histologic types

A)Squamous cell carcinoma :((20%) ,arise in the central/hilar lung regions. highly associated with tobacco smoking. genetic abberations are mostly chromosome deletions involving tumour suppressor gene loci ( 3p,9p site of the CDKN2A gene and 17p site of TP53gene).

• Precursor lesions include squamous dysplasia (or metaplasia) which transforms into carcinoma in situ. This phase may last for several years, during this period atypical cells may be identified on cytologic sputum smears or bronchial lavage .
• Histologic features; malignant squamous cells with presence of keratinisation and or intercellular bridges.

• B)Adenocarcinomas are about 38% of all lung cancers; more often arise in the peripheral lung. They arise due to gain of function mutation in multiple genes encoding tyrosine kinase receptors. these are EGFR ,ALK,ROS,MET,RET genes. Adenocarcinomas without tyrosine kinase gene mutations usually have mutations in the KRAS gene. Precursor lesions are atypical adenomatous hyperplasia adenocarcinoma in situ. These may or may not progress to invasive cancers.

LUNG CANCER

• Adenocarcinomas are characterised by glandular differentiation or mucin production. Several growth patterns include;
• Papilary
• Acinar
• Lepidic
• Micropapillary
• Solid with mucinous differentiation

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LUNG CANCER

• C) Small cell carcinoma;14% of all lung cancers they usually arise from the periphery or major bronchi of the lung.
• It has a strong relationship to smoking ,a few however may occur in non smokers.
• SCLC s are the most aggressive lung cancers which are associated with ectopic hormone production.
• P53 and Rb genes are frequently mutated
• About 90% of SCLCs express the BCL2 gene.
• Histologically they are composed of small cells with neurosecretory granules.

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LUNG CANCER

• LARGE CELL CARCINOMA:
• They actually represent adenocarcinomas and squamous cell carcinomas that are so undifferentiated to the extent that they can no longer be recognised by light microscopy.
• Histologically ,they are large cells with prominent nucleoli and moderate cytoplasm.

LUNG CANCER

• SECONDARY PATHOLOGY
• Several secondary diseases of the lungs occur due to the presence of lung cancer because of the anatomical changes in the lung substance.
• 1)marked focal emphysema: due to partial obstruction
• 2)atelectasis: due to total obstruction.
• 3)Severe suppurative bronchitis, Ulcerative bronchitis, bronchiectasis: due to impaired drainage of the airways.
• Pulmonary abscesses: may be due to a silent carcinoma that has initiated inflammation
• 4)Superior vena cava syndrome: compression of the superior vena cava by lung cancer leading to edema of the head and arm and eventually circulatory compromise.
• 5)Extension to pericardial sac- pericarditis
• 6)Extension to the pleural sac-pleuritis.

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PARANEOPLASTIC SYNDROME

• Lung cancers are associated with several paraneoplastic syndromes,(due to production of hormones and hormone-like factors )patients may experience symptoms long before the pulmonary lesion is detected.
• ADH
• ACTH
• Parathormone
• Parathyroid related peptide
• Prostaglandin E
• Calcitonin Serotonin and bradykinin

PARANEOPLASTIC SYNDROME

• ACTH and ADH are associated with mainly small cell carcinomas.
• Parathormone ,parathyroid related peptide produce hypercalcemias and are mostly squamous cell carcinomas.
• Small cell carcinomas : carcinoid syndromes.
• Lambert –Eaton Myasthenic Syndrome: autoantibodies directed against neuronal calcium channels.
• Peripheral neuropathy.
• Leukaemoid reactions
• Hypertrophic pulmonary osteoarthropathy.
• Pancoast tumours: apical lung cancers that invade the neural structures around trachea including the cervical sympathetic plexus .These result into severe pain in the distribution of the ulnar nerve and also Horners syndrome (ptosis, anhydrosis, miosis, enophthalmos).

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PLEURA

• PLEURAL EFFUSION
• Pleural effusion is a common manifestation of both primary and secondary pleural diseases, which may be inflammatory or noninflammatory.
• Normally, no more than 15 mL of serous, relatively acellular, clear fluid lubricates the pleural surface. Accumulation of pleural fluid occurs in the following settings:

• Increased hydrostatic pressure, as in congestive heart failure

• Increased vascular permeability, as in pneumonia

• Decreased osmotic pressure, as in nephrotic syndrome

• Increased intrapleural negative pressure, as in atelectasis

• Decreased lymphatic drainage, as in mediastinal carcinomatosis Inflammatory Pleural Effusion.

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Inflammatory pleural effusion

• . The most common causes of pleuritis are disorders associated with inflammation of the underlying lung, they mostly give rise to serous,serofibrinous and fibrinous pleuritis such as :
• tuberculosis,
• pneumonia, lung infarction,
• lung abscess, bronchiectasis.
• Rheumatoid arthritis, systemic lupus erythematosus,
• uremia, diffuse systemic infections,
• metastatic involvement of the pleura can also cause serous or serofibrinous pleuritis.

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Inflammatory pleural effusion

• Empyema
• Hemorrhagic pleuritis manifested by sanguineous inflammatory exudates is infrequent and is most often associated with hemorrhagic diatheses, rickettsial infections, and neoplastic involvement of the pleural cavities.

Non inflammatory pleural effusion

• Hydrothorax: most common cause of hydrothorax is heart failure, and for this reason it is usually accompanied by pulmonary congestion and edema.
• Hydrothorax may also be seen in any other systemic disease associated with generalized edema, such as patients with renal failure or cirrhosis of the liver.
• Hemothorax:The escape of blood into the pleural cavity.
• its the most common complication of trauma.
• may also result from the rupture of an aortic aneurysm (fatal).

• Chylothorax is an accumulation of milky fluid, usually of lymphatic origin, in the pleural cavity.
• Chyle is milky white because it contains finely emulsified fats. Chylothorax is most often caused by thoracic duct trauma or by obstruction of a major lymphatic duct, usually by a malignancy

PNEUMOTHORAX

• Pneumothorax refers to air or gas in the pleural cavities and is most commonly associated with emphysema, asthma and tuberculosis.

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• Spontaneous pneumothorax may complicate any form of pulmonary disease that causes emphysematous changes.
• Traumatic pneumothorax is usually caused by some perforating injury to the chest wall.

PLEURAL TUMOURS

• Solitary fibrous tumours
• mesothelioma

MESOTHELIOMA

• . Thoracic mesothelioma arises from either the visceral or the parietal pleura.its presently on the increase among people with heavy exposure to asbestos (asbestosis-pneumoconiosis.)