COPD.pdf

PATHOLOGY OF RESPIRATORY SYSTEM ASS.PROF DR. SURA EJAM Objectives ▪ 1.To define and classify the types of atelectasis. ▪ 2- To define the chronic obstructive airway diseases ▪ 2. To study the gross & microscopical features of these lesions and correlate them with signs & symptoms ▪ Atele...

PATHOLOGY OF RESPIRATORY SYSTEM ASS.PROF DR. SURA EJAM Objectives ▪ 1.To define and classify the types of atelectasis. ▪ 2- To define the chronic obstructive airway diseases ▪ 2. To study the gross & microscopical features of these lesions and correlate them with signs & symptoms ▪ Atelectasis ▪ Definition : is loss of lung volume caused ▪ by inadequate expansion of airspaces. It is associated with shunting of inadequately oxygenated blood from pulmonary arteries into pulmonary veins, thus giving rise to a ventilation – perfusion imbalance and hypoxia ▪ Types : ▪ 1- Resorption Atelectasis : ▪ It occurs when an obstruction prevents air from reaching distal airways, the air already present gradually becomes absorbed and alveolar collapse follows. The most common cause of this type is obstruction of bronchus by mucus plug, other causes include foreign body, tumor, enlarged lymph nodes. ▪ 2- Compression Atelectasis : It is associated with accumulations of fluid, blood ▪ and air within the plural cavity, which mechanically collapse the adjacent lung,, this is frequent occurrence with plural effusions caused most commonly with congestive heart failure ▪ 3-Microatelectasis : ▪ It is a generalized loss of lung expansion caused by a complex set of events, the most important of which is loss of surfactant in both adult and neonatal respiratory distress syndrome. ▪ 4- Contraction Atelectasis : ▪ It occurs when either local or generalized fibrotic changes in the lung or pleura hamper expansion and increase elastic recoil during expiration.  Chronic Obstructive Airway Diseases (COPD) COPD is a group of disorders characterized by airflow obstruction. Their characteristics include a marked decreased in first second forced expiratory volume (FEV1) and increased or normal forced vital capacity (FVC), resulting in decreased FEV1 : FVC ratio. COPD include : 1- Asthma. 2- Emphysema. 3-Chronic Bronchitis. 4- Bronchiectasis air way obstruction can be caused by 1- goblet cell hyperplasia & mucus plug 2-inflammatory edema 3- muscle hypertrophy Asthma Definition : is characterized by episodic , reversible bronchospasm resulting form an exaggerated bronchoconstricter response to various stimuli. ▪ Classification of asthma: 1. 1. Atopic Asthma :- This most common type of asthma is a classic example of type I IgE-mediated hypersensitivity reaction,. The disease usually begins in childhood and is triggered by environmental allergens, such as dusts, pollens, roach or animal dander, and foods. 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 reaction. 2. Non Atopic Asthma The second group of ▪ individuals with asthma does 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) are common triggers in non-atopic asthma. In these patients hyperirritability of the bronchial tree probably underlies their asthma. Inhaled air pollutants, such as sulfur dioxide, ozone, and nitrogen dioxide, may also contribute to the chronic airway inflammation and hyperreactivity that are present in some cases. 3.Drug induced Asthma ▪ Several pharmacologic agents provoke asthma. ▪ Aspirin-sensitive asthma is an uncommon yet fascinating type, occurring in individuals with recurrent rhinitis and nasal polyps. These individuals are exquisitely sensitive to small doses of aspirin as well as other nonsteroidal anti-inflammatory 4.Occupational Asthma This form of asthma is ▪ stimulated by fumes (epoxy resins, plastics), organic and chemical dusts (wood, cotton, platinum), gases (toluene), and other chemicals (formaldehyde, penicillin products). Minute quantities of chemicals are required to induce the attack, which usually occurs after repeated exposure. Pathogenesis we discuss pathogenesis of atopic asthma because ▪ it is most common. The common dominator underlying asthma is an ▪ airway hyperresposiveness , bronchial inflammation is the substrate of hyperresposiveness , the cause of inflammation in atopic asthma is type I hypersensitivity reaction which is driven by sensitization of CD4 cells of TH2 type. TH2 cells release cytokines (IL4,5,13 ) which ▪ favor synthesis of IgE, growth of mast cells and activation of eosinophils 1- role of IgE:- ▪ IgE bind to the foreign antigen and then it will bind to mast ▪ cells leading to release mast cell mediators like histamine. 2- role of mast cells :- the initial triggering of mast cells occur ▪ in mucosal surface , the resultant mediators release opens mucosal intercellular junctions allowing penetration of antigens to more numerous mucosal mast cells , in addition to direct stimulators of parasympathetic receptors provokes reflex bronchospasm. Examples of mast cells mediators ▪ : Histamine , IL4 , IL5prostaglandin E2 ,D2 , F2α , leukotrienes ▪...,etc ▪ 3- Role of eosinophils:- Eosinophils contain the following : A- major basic protein and eosinophilic ▪ cationic protein which are directly toxic to the epithelial cells B- eosinophilic peroxidase causes tissue ▪ damage through oxidative stress. C- activated eosinophils are rich in leukotriene ▪ C4 and platelet activating factors.  Asthma ▪ Definition : is characterized by episodic , reversible bronchospasm resulting form an exaggerated bronchoconstricter response to various stimuli. ▪ Morphology: ▪ Grossly :- the lung are over distended with small area of atelectasis , the most important striking finding macroscopically is the occlusion of bronchi and bronchioles by thick tenacious mucous plug (is formed of inspissated mucus {fluid ,neutrophil, epithelial cells ) ▪ Microscopically:- ▪ 1- edema , hyperemia and inflammatory infiltrate in the bronchial walls (eosinophils 5-50% of cellular infiltrate , mast cells , basophils , macrophage and neutrophils. ▪ 2- increase in size of submucosal mucous glands ( or increase of goblet cells in the bronchiolar epithelium). ▪ 3- patchy necrosis and shedding. ▪ 4- hypertrophy and hyperplasia of smooth muscles in the bronchial wall Mucus plugs :This cast of the bronchial tree is formed of inspissated mucus ,thick consists of {fluid ,neutrophil, epithelial cells } and was coughed up by a patient during an asthmatic attack.. There are the hyperinflated or overdistended lungs of a patient who died with status asthmaticu Clinical features ▪ -The classic acute asthmatic attack lasts up to several ▪ hours. In some patients these symptoms of chest tightness, dyspnea, wheezing, and cough with or without sputum production, persist at a low level constantly. -In its most severe form, status asthmaticus, the severe acute paroxysm persists for days and even weeks, and under these circumstances airflow obstruction might be so extreme as to cause severe cyanosis and even death -Up to 50% of childhood asthma remits in adolescence ▪ only to return in adulthood in a significant number of patients. -In other cases there is a variable decline in lung ▪ function  ▪ Emphysema : - ``▪ Definition: is characterized by permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls.. Types of emphysema:- ▪ 1- centriacinar ( centrlobular) emphysema: ▪ In which the central and proximal part of acinus are affected ( formed by respiratory bronchioles ) ▪ The lesions are more sever and common in upper lobes particularly in apical airspaces or segments. emphysematous spaces often contain large amounts of black pigment In sever centriacinar emphysema , the distal acinus also becomes involved. ▪ This type of emphysema is most commonly seen as a consequence of cigarette smoking and often in association with chronic bronchitis. 2- panacinar emphysema : ▪ In this type of emphysema, the acini are uniformly ▪ enlarged from the level of the respiratory bronchiole to the terminal blind alveoli The prefix “pan” refers to the entire acinus but not to ▪ the entire lung. 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 It is the type of emphysema that occurs in α1- ▪ antitrypsin deficiency. 3- Distal Acinar (paraseptal) Emphysema In this form, the proximal portion of the acinus is normal but the distal part is dominantly involved. The emphysema is more striking adjacent to the pleural margin of the lobules. It occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lung. It leads to formation of bullae and underlies many cases of spontaneous pneumothorax. 4-Airspace Enlargement with Fibrosis (Irregular Emphysema) Irregular emphysema, so named because the acinus is irregularly involved, is almost invariably associated with scarring. Thus, it may be the most common form of emphysema, because careful search of most lungs at autopsy shows one or more scars from a healed inflammatory process. In most instances, these foci of irregular emphysema are asymptomatic and clinically insignificant 5 ▪ Pathogenesis : ▪ Emphysema arising as a consequence of two critical imbalances : protease -antiprotease and oxidant – antioxidant imbalances. ▪ The protease- antiprotease imbalance is the underlying cause of pulmonary emphysema in patient with genetic deficiency of α1 – antitrypsin ▪. ▪ α1 – antitrypsin normally present in serum , tissue fluids and macrophages is a major inhibitor of protease (elastase) secreted by neutrophils during inflammation leading to elastic tissue digestion. ▪ α1-antitrypsin is encoded by codominantly expressed ▪ genes on the proteinase inhibitor (Pi) locus on chromosome 14. The Pi locus is extremely polymorphic, with many different alleles. Most common is the normal (M) allele and the corresponding phenotype. Approximately 0.012% of the US population is homozygous for the Z allele, associated with markedly decreased serum levels of α1antitrypsin. ▪ The following sequence is postulated in panacinar emphysema : ▪ 1. Neutrophils (the principal source of cellular proteases) are normally sequestered in peripheral capillaries, including those in the lung, and a few gain access to the alveolar spaces. ▪ 2. Any stimulus that increases either the number of leukocytes (neutrophils and macrophages) in the lung or the release of their protease-containing granules increases proteolytic activity. ▪ 3.With low levels of serum α1-antitrypsin, elastic tissue destruction is unchecked and emphysema results. ▪ In smoking: ▪ 1- the direct chemoattractant effect of nicotine and effect of reactive oxygen species in smoke These activate the transcription factor NF-κB, which switches on genes that encode TNF and chemokines, including IL-8. These, in turn, attract and activate neutrophils.. 2-With accumulation of neutrophils which release ▪ their protease ( elastase ) leading to tissue damage because of oxidative injury of smoking that lead to inactivation of α1 – antitrypsin. ▪ 3- smoking also enhances elastic activity in macrophage ▪ which is not inhibited by α1 – antitrypsin 4- the abundant reactive oxygen species will deplete the ▪ antioxidants tat are normally present in the lung to keep oxidative damage to a minimum thereby inciting tissue damage. the loss of elastic tissue in the walls of alveoli ▪ that surround respiratory bronchioles reduces radial traction and thus causes the respiratory bronchioles to collapse during expiration. ▪ Morphology: ▪ Grossly : the lung in panacinar emphysema when well developed , appears pale, voluminous , and obscure the heart when anterior chest wall removed at autopsy. ▪ In centriacinar emphysema , the lungs are deeper pink and less voluminous. ▪ In extreme cases, emphysematous bullae may be visible. ▪ Microscopically : ▪ 1- there is thinning and destruction of alveolar walls. with advanced disease , adjacent alveoli become confluent creating large airspaces. ▪ 2- terminal bronchi and bronchioles may be deformed because of loss of septa that help tether those structure in parenchyma. ▪ There is also fibrosis of bronchioles with evidence od bronchitis and bronchiolitis ▪ Inflammatory changes in small airways were described earlier emphysema.:numerous large bullae apparent on the surface of the lungs in a patient dying. Bullae are large dilated airspaces that bulge out with pale enlarge lungs. On cut section of the lung, the dilated airspaces with a are seen. Although there tends to be some scarring with time becaause of uperimposed infections, Microscopical picture of emphysema.at high magnification, destruction of alveolar walls, airspaces are dilated.  Clinical ▪ Features: 1- Dyspnea is usually the first symptom. In patient with no "bronchitic" component , barrel-chest is a prominent feature. Because of dyspnea , there is adequate oxygenation of Hb. and patient called ( pink puffers ). 2- in patient with underlying bronchitis , there are cough and wheezing with purulent sputum with loss of dyspnea lead to hypoxia patient called blue bloaters 3- weight loss is common and may be so sever as to suggest a hidden malignancy and the patient may die from: 1- respiratory failure 2- right sided heart failure. ▪ Chronic bronchitis : ▪ Definition : - is persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. ▪ It is common in cigarette smokers and people who expose to air pollutants , such as sulfur dioxide and nitrogen dioxide. When persistent for years, it may ▪ (1) progress to COPD, ▪ (2) lead to cor pulmonale and heart failure, or ▪ (3) cause atypical metaplasia and dysplasia of the respiratory epithelium, providing a rich soil for cancerous transformation ▪ Pathogenesis : ▪ The primary or initiating factor in the genesis of chronic bronchitis seems to be long-standing irritation by inhaled substances such as tobacco smoke (90% of patients are smokers), and dust from grain, cotton, and silica. The earliest feature of chronic bronchitis is hypersecretion of mucus in the large airways, associated with hypertrophy of the submucosal glands in the trachea and bronchi. Proteases released from neutrophils, such as neutrophil elastase and cathepsin, and matrix metalloproteinases, stimulate this mucus hypersecretion. As chronic bronchitis persists, there is also a marked ▪ increase in goblet cells of small airways—small bronchi and bronchioles—leading to excessive mucus production that contributes to airway obstruction. It is thought that both the submucosal gland hypertrophy and the increase in goblet cells are protective metaplastic reactions against tobacco smoke or other pollutants (e.g., sulfur dioxide and nitrogen dioxide). 2- infection is often present but plays a secondary ▪ role chiefly by maintaining and exacerbating of symptoms. ▪ Morphology : - ▪ Grossly : the mucosal lining of larger airways is usually hyperemic and swollen and edema fluid. It is often covered by a layer if mucopurulent sputum. ▪ Microscopically: A. Enlargement of mucous secreting glands in submucosal layer. B. Increase number of goblet cells in lining epithelium with concomitant loss of ciliated epithelial cells. C. Squamous metaplasia frequently develops followed by dysplastic changes. A sequence of events that may lead to evolution of bronchogenic carcinoma. D. A variable density of inflammatory cells largely mononuclear but sometimes admixed with neutrophils is frequently present in the bronchial mucosa , the tissue neutrophilia increases during bronchitic exacerbations. Unlike asthma , eosinophils don not constitute prominent component.. Chronic bronchitis ,increased numbers of chronic inflammatory cells in the sub mucosa, hyperatrophy and hyperplasia of submucoal glands with metaplastic changes.  Clinical features : ▪ 1- prominent cough and production of sputum ▪ may persist without ventilator dysfunction and some patients may progress to chronic obstructive disease with hypoxemia and cyanosis. 2- chronic bronchitis is complicated by ▪ recurrent infection , pulmonary hypertension and cardiac failure. ▪ Bronchiectasis :– ▪ Definition: is the permanent dilatation of bronchi and bronchioles caused by destruction of muscle and supporting elastic tissue resulting from or associated with chronic necrotizing infections. It is not a primary disease but rather is secondary to persisting infection or obstruction caused by variety of conditions. The condition that most commonly predispose to bronchiectasis include the following: ▪ 1- Bronchial obstruction: Common causes are tumors, foreign bodies, and occasionally impaction of mucus. Under these conditions, the bronchiectasis is localized to the obstructed lung segment. Bronchiectasis can also complicate atopic asthma 2- congenital or hereditary conditions ▪ A- In cystic fibrosis, widespread severe bronchiectasis results from obstruction and infection caused by the secretion of abnormally viscid mucus. ▪ B- In immunodeficiency states, particularly immunoglobulindeficiencies, bronchiectasis is prone to develop because of an increased susceptibility to repeated bacterial infection ▪ C- Kartagener syndrome, an autosomal recessive disorder, is frequently associated with bronchiectasis. Structural abnormalities of the cilia impair mucociliary clearance, leading to persistent pulmonary infections. ▪ (Kartagener syndrome ) ( bronchiectasis, sinusitis, dextrocardia and male sterility) ▪ 3- Necrotizing, or suppurative, pneumonia, particularly with virulent organisms such as Staphylococcus aureus or Klebsiella spp., may predispose to bronchiectasis. ▪ Post-tubercular bronchiectasis continues to be a significant cause of morbidity in endemic areas. ▪ viruses (adenovirus, influenza virus, human immunodeficiency virus [HIV]), and fungi (Aspergillus species) ▪ Clinical features: ▪ 1- persistent cough with expectoration of mucopurulent sputum. The sputum may contain flecks of blood; frank hemoptysis can occur. ▪ 2- clubbing of fingers. ▪ 3- hypoxemia , hypercapnia pulmonary hypertension and core pulmonale. ▪ 4- metastatic brain abscesses and reactive amyloidosis are less frequent complications. ▪ Pathogenesis : - ▪ Two processes are critical in pathogenesis pf bronchiectasis : ▪ 1- obstruction. ▪ 2- chronic persistent infection ▪ Either of these two processes may come first. Normal clearance mechanisms are hampered by obstruction, so secondary infection soon follows; conversely, chronic infection causing damage to bronchial walls and obstructive secretion leading to weakening and dilation Morphology :- ▪ Grossly :- bronchiectatic involvement of lungs usually affects the lower lobes bilaterally , particularly those air passages that are more vertical. The most sever involvement is found in the more distal bronchi and bronchioles. The airways may be dilated to as much as 4 times their usual diameter. Microscopically ▪ : The histologic findings vary with the activity and chronicity of the disease. In the full-blown picture of disease, an intense acute and chronic inflammatory exudate within the walls of the bronchi and bronchioles and the desquamation of lining epithelium cause extensive areas of ulceration. Fibrosis of bronchial and bronchiolar walls develop in more chronic cases. When healing occurs , the lining epithelium may regenerate completely , however so much injury has occurred that abnormal dilation and scarring has occurred. Necrosis destroys the bronchial and bronchiolar walls and forms lung abscess.  Microscopically ▪ : The histologic findings vary with the activity and chronicity of the disease. In the full-blown picture of disease, an intense acute and chronic inflammatory exudate within the walls of the bronchi and bronchioles and the desquamation of lining epithelium cause extensive areas of ulceration. Fibrosis of bronchial and bronchiolar walls develop in more chronic cases. Necrosis destroys the bronchial and bronchiolar walls Bronchiectasis :a closer view demonstrates the focal area of dilated bronchi with bronchiectasis. tends to be localized with disease processes such as neoplasms and aspirated foreign bodies.