Respiratory pathology Flashcards
What is the function of the lungs
The midline trachea develops jnto what?
The right lung divides into what?
The left lung divided into what?
These teo divisions give rise to what?
Main bronchi gives rise to what? And how are they distinguished from bronchi?
Additional branching of what the main bronchi gives rise to leads to what?
What is acinus ?
Pulmonary acini are composed of what and where do they branch into?
Where is the site of gaseous exchange?
The microscopic structure of the alveolar walls consist of what four things?
Alveolar epithelium contains a continuous layer of how many principal cell types and name them? What are their functions?
What perforates alveolar walls and this permits passage of what?
Primary lung diseases van be broadly divided into those affecting which three places?
In reality, disease in one compartment often causes secondary alterations of morphology and function in other areas.
True or false
The major function of the lung is to replenish oxygen and excrete carbon dioxide from blood.
The midline trachea develops two lateral outpocketings, the lung buds. The right lung bud eventu- ally divides into three main bronchi, and the left into two main bronchi, thus giving rise to three lobes on the right and two on the left. The main bronchi branch dichoto- mously, giving rise to progressively smaller airways, termed bronchioles, which are distinguished from bronchi by the lack of cartilage and submucosal glands within their walls. Additional branching of bronchioles leads to terminal bronchioles; the part of the lung distal to the terminal bron- chiole is called an acinus. Pulmonary acini are composed of respiratory bronchioles (emanating from the terminal bronchiole) that proceed into alveolar ducts, which immedi- ately branch into alveolar sacs, the blind ends of the respira- tory passages, whose walls are formed entirely of alveoli, the ultimate site of gas exchange. The microscopic structure of the alveolar walls (or alveolar septa) consists of the following components, proceeding from blood to air (Fig. 12–1):
• The capillary endothelium and basement membrane.
• The pulmonary interstitium is composed of fine elastic fibers, small bundles of collagen, a few fibroblast-like cells, smooth muscle cells, mast cells, and rare mono- nuclear cells. It is most prominent in thicker portions of
the alveolar septum.
• Alveolar epithelium contains a continuous layer of
two principal cell types: flattened, platelike type I pneumocytes covering 95% of the alveolar surface and rounded type II pneumocytes. The latter synthesize pul- monary surfactant and are the main cell type involved in repair of alveolar epithelium after damage to type I pneumocytes. The alveolar walls are not solid but are perforated by numerous pores of Kohn, which permit passage of air, bacteria, and exudates between adjacent alveoli.
• A few alveolar macrophages usually lie free within the alveolar space. In the adult, these macrophages often contain phagocytosed carbon particles.
There are multiple primary lung diseases that can broadly be divided into those primarily affecting (1) the airways, shown.
(2) the interstitium, and (3) the pulmonary vascular system. This division into discrete compartments is, of course, deceptively neat.
What is another name for atelectasis and what is atelectasis
What does it result in?
What is the basis of the classification of atelectasis?
What are the forms of atelectasis classified into?
When do these forms occur or what are they usually associated eith?
Obstruction of a bronchus by a mucous or mucopurulent plug is a commin cause of which type of atelectasis?
This obstruction may complicate which diseases particularly in children?
Which form of atelectasis is a frequent occurence eith pleural effusion caused mostly by CHF?
Basal atelectasis due to elevated position of the diaphragm commonly occurs in which three patients?
Is atelectasis reversible?
When will it be irreversible
The condition should be treated promptly to prevent what two things?
Atelectasis, also known as collapse, is loss of lung volume caused by inadequate expansion of air spaces. It results in shunting of inadequately oxygenated blood from pulmo- nary arteries into veins, thus giving rise to a ventilation- perfusion imbalance and hypoxia. On the basis of the underlying mechanism or the distribution of alveolar col- lapse, atelectasis is classified into three forms (Fig. 12–2).
• Resorption atelectasis. Resorption atelectasis occurs when an obstruction prevents air from reaching distal airways. The air already present gradually becomes absorbed, and alveolar collapse follows. Depending on the level of airway obstruction, an entire lung, a complete lobe, or one or more segments may be involved. The most common cause of resorption collapse is obstruction of a bronchus by a mucous or mucopurulent plug. This fre- quently occurs postoperatively but also may complicate bronchial asthma, bronchiectasis, chronic bronchitis, tumor, or foreign body aspiration, particularly in children.
• Compression atelectasis. Compression atelectasis (some- times called passive or relaxation atelectasis) is usually associated with accumulation of fluid, blood, or air within the pleural cavity, which mechanically collapses the adjacent lung. This is a frequent occurrence with pleural effusion, caused most commonly by congestive heart failure (CHF). Leakage of air into the pleural cavity (pneumothorax) also leads to compression atelectasis. Basal atelectasis resulting from the elevated position of the diaphragm commonly occurs in bedridden patients, in patients with ascites, and during and after surgery.
• Contraction atelectasis. Contraction (or cicatrization) ate- lectasis occurs when either local or generalized fibrotic changes in the lung or pleura hamper expansion and increase elastic recoil during expiration.
Atelectasis (except when caused by contraction) is poten- tially reversible and should be treated promptly to prevent hypoxemia and superimposed infection of the collapsed lung.
In this form of atelectasis,fluid or air prevents full expansion of the area of the lung jts in leading to collapse. What form of atelectasis is this?
In this form of atelectasis the affected lung is fibrosed and has lost its elasticity so its not aboe to expand well leading to collapse but there’s increased recoil when uou breathe out
What form of atelectasis is this?
Which bronchi is steeper and wider and its easy for aspirated materials to get in there?
Which fissures divide the right lung into three? Which fissure divides the left lung into two
What us the functional unit for gaseous exchange
What does the acinus comprise of
What is the function of surfactant
Type 2 cells can turn themselves into type 1 true or false
Atelectasis can be congenital or acquired true or false?
Name three common and less common congenital lung diseases
Whats the difference between hypoxia and hypoxemia
Compression atelectasis
Contraction atelectasis
Right lung
Oblique and horizontal fissures
Oblique fissure
Acinus
Respiratory bronchioles,alveolar sacs,alveolar duct
It provides surface tension that keeps the integrity of the alveolar sacs
True
True
Common:
Pulmonary hypoplasia
Foregut cysts
Pulmonary sequestration
Less vommon:
Vascular anomalies
Congenital lobar overinflation
Bronchial and tracheal anomalies
Hypoxia:low oxygen in blood
Hypoxemia:low oxygen saturation in the blood
Check well cuz im not sure of this definition
What is acute lung injury
Clinically acute lung injury manifests as what three symptoms
Pulmonary inflitrates in acute lung injury are usually caused by what?
Acute lung injury can progress ti what?
Left sided heart failure can present with loss of the costeophrenic angle so if theres this loss but theres not heart failure think of acute lung injury
True or false
With the clinical disorders associated with acute lung injury or acute respiratory distress syndrome
What are common and unvommon causes of direct lung injury or indirect lung injury
The term acute lung injury encompasses a spectrum of bilat- eral pulmonary damage (endothelial and epithelial), which can be initiated by numerous conditions.
Clinically, acute lung injury manifests as (1) acute onset of dyspnea, (2) decreased arterial oxygen pressure (hypoxemia), and (3) development of bilateral pulmonary infiltrates on the chest radiograph, all in the absence of clinical evidence of primary left-sided heart failure. Since the pulmonary infiltrates in acute lung injury are usually caused by damage to the alveolar capillary membrane, rather than by left-sided heart failure (Chapter 10), such accumulations constitute an example of noncardiogenic pulmonary edema. Acute lung injury can progress to the more severe acute respiratory distress syndrome,
True
Direct lung injury:
Common Causes
Pneumonia
Aspiration of gastric contents
Uncommon causes: Pulmonary contusion Fat embolism Near-drowning Inhalational injury Reperfusion injury after lung transplantation
Indirect lung injury:
Common causes:
Sepsis
Severe trauma with shock
Uncommon Causes Cardiopulmonary bypass Acute pancreatitis Drug overdose Transfusion of blood products Uremia
What is ARDS
Usual course of this disease is characterized by what signs?
Whats the histologic manifestation of this disease?
ARDS can occur in a multitude of clinical settings and is associated with either direct injury to the lung or indirect injury in the setting of a systemic process
True or false
What is respiratory distress syndrome of the newborn caused by?
What is the gross morphology in the acute phase of ARDS and what’s the histologic appearance of the lungs in ARDS
What’s yhe most characteristic finding in the histologic appearance of the lungs
Hyaline membranes contain what?
In the organizing stage,what is seen?
With the appearance,resolution is unusual; more commonly, there is organization of the fibrin exudates, with resultant intra-alveolar fibrosis.
True or false
Marked thickening of yhe alveolar septa ensues and is caused by??
Healing stage is marked by ehat features?
Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by diffuse alveolar capillary and epithe- lial damage.
The usual course is characterized by rapid onset of life-threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia that is refractory to oxygen therapy and may progress to multisystem organ failure. The histologic manifestation of ARDS in the lungs is known as diffuse alveolar damage (DAD).
It should be recalled that respiratory distress syndrome of the newborn is pathoge- netically distinct; it is caused by a primary deficiency of surfactant.
In the acute phase of ARDS, the lungs are dark red, firm, airless, and heavy. Microscopic examination reveals capillary congestion, necrosis of alveolar epithelial cells, interstitial and intra-alveolar edema and hemorrhage, and (particularly with sepsis) collections of neutrophils in capillaries. The most characteristic finding is the presence of hyaline mem- branes, particularly lining the distended alveolar ducts (Fig. 12–4). Such membranes consist of fibrin-rich edema fluid admixed with remnants of necrotic epithelial cells. Overall, the picture is remarkably similar to that seen in respiratory distress syndrome in the newborn (Chapter 6). In the orga- nizing stage, vigorous proliferation of type II pneumocytes occurs in an attempt to regenerate the alveolar lining.
True
Marked thickening of the alveolar septa ensues, caused by prolifera- tion of interstitial cells and deposition of collagen.
The healing stage is marked by resorption of hyaline membranes with thickening of alveolar septa containing inflammatory cells, fibroblasts, and collagen. Numerous reactive type II pneumocytes also are seen at this stage (arrows), associated with regeneration and repair.
With the pathogenesis of ARDS ,the alveolar capillary membrane is formed by which two separate barriers?
What happens to these barriers in ARDS ?
What are the four acute consequences of damage to the alveolar capillary membrane
What is the cause of lung injury in ARDS
What happens after thirty minutes of acute insult?
Which chemokines come to play in acute ARDS and what are their functions?
What is the function of neutrophils in ARDS?
Histological exam of lungs in ARDS shows what?
Activated neutrophils release which products
What causes the alveolar unit to not expand?
Destructive forces unleashed by neutrophils can be counteracted by what?
What determines the degree of tissue injury and clinical severity of ARDS?
What happens to neutrophils under the influence of proinflammatory cytokines?
What happens to activated neutrophils and where are they activated?
Factord that neutrophils release contribute to whatv
Release of macrophage derived fibrogenic cytokines stimulate what?
A.In Acute Respiratory Distress Syndrome,the integrity of the microvascular endothelium barrier and the alveolar epithelium barrier are com- promised by either endothelial or epithelial injury, or, most commonly, both. The damage to the alveolar capillary membrane ,which comprises of the microvascular endothelium barrier and the alveolar epithelium barrier ,causes acute consequences such as increased vascular permeability and alveolar flooding, loss of diffusion capacity, and widespread surfactant abnormalities which are caused by damage to type II pneumocytes . In Acute Respiratory Distress Syndrome , injury to the lung is caused by an imbalance of pro-inflammatory and anti-inflammatory media- tors. After an acute injury to the lung, there is increased synthesis of interleukin 8 (IL-8), by pulmonary macrophages . Release of this and mediators, such as Interleukin-1 and tumor necrosis factor (TNF), results to endothelial activation as well as sequestration and activation of neutrophils in pulmonary capillaries. Activation of the neutrophils causes a release of oxidants,platelet activating factor,leukotrienes and proteases and these released products cause damage to the alveolar capillary membrane. Damage to this membrane causes vascular leafiness and loss of surfactant which then prevents the alveolar unit from expanding properly. On Histologic examination of the lungs early in the disease process there are increased numbers of neutrophils within the vascular space, the interstitium, and the alveoli. Of note, the destructive forces unleashed by neutrophils can be counteracted by an array of endoge- nous antiproteases, antioxidants, and anti-inflammatory cyto- kines (e.g., IL-10) that are upregulated by pro-inflammatory cytokines. In the end, it is the balance between the destruc- tive and protective factors that determines the degree of tissue injury and clinical severity of the disease
The normal alveolus (left), compared with the injured alveolus in the early phase of acute lung injury and the acute respiratory distress syndrome. Under the influence of proinflammatory cytokines such as interleukins IL-8 and IL-1 and tumor necrosis factor (TNF) (released by macro- phages), neutrophils initially undergo sequestration in the pulmonary microvasculature, followed by margination and egress into the alveolar space, where they undergo activation. Activated neutrophils release a variety of factors such as leukotrienes, oxidants, proteases, and platelet-activating factor (PAF), which contribute to local tissue damage, accumulation of edema fluid in the air spaces, surfactant inactivation, and hyaline membrane formation. Subsequently, the release of macrophage-derived fibrogenic cytokines such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PGDF) stimulate fibroblast growth and collagen deposition associated with the healing phase of injury
With the clinical features of ARDS, most patients develop ARDS within how many hours of the initiating insult?
What are the predictors of poor prognosis in ARDS
What two things can happen to patients who survive the acute stage ?
Approximately 85% of patients develop the clinical syn- drome of acute lung injury or ARDS within 72 hours of the initiating insult. Predictors of poor prognosis include advanced age, underlying bacteremia (sepsis), and the development of multisystem (especially cardiac, renal, or hepatic) failure. Should the patient survive the acute stage, diffuse inter- stitial fibrosis may occur, with continued compromise of respiratory function. However, in most patients who survive the acute insult and are spared the chronic sequelae, normal respiratory function returns within 6 to 12 months.
Summarize what youve learnt about ARDS
(What is ARDS ,state the major player in the pathogenesis of ARDS and what does it cause? Whats the characteristic histologic picture of the lung in ARDs?
Acute Respiratory Distress Syndrome
• ARDS is a clinical syndrome of progressive respiratory insufficiency caused by diffuse alveolar damage in the setting of sepsis, severe trauma, or diffuse pulmonary infection.
• Neutrophils and their products have a crucial role in the pathogenesis of ARDS by causing endothelial and epithelial injury.
• The characteristic histologic picture is that of alveolar edema, epithelial necrosis, accumulation of neutrophils, and presence of hyaline membranes lining the alveolar ducts.
Diffuse pulmonary diseases can be classified into two categories ,name them and what they are characterized byz
What are the four major diffuse obstructive disorders?
In patients with obstructive disorders,forced vital capacity is what?
Expiratory flow rate is measured as what? And is significantly increased or decreased?
Ratio of forced expiratory volune to forced vital capacity is what in obstructive disorders?
Expiratory obstruction may result from which two things?
FVC is reduced and FEV is normal or reduced proportionately meaning ratio if FEV to FVC is near normal in which diseases?
The restrictive defect occurs in which two general conditions?
Name three chronic restrictive diseases ?
With restrictive disorders the ratio means you can take in much or less and you can bring out much or less while is obstructive the ratio means you breathe in much but you cant bring out much
True ir false
What us inspiratiry capacity
Diffuse pulmonary diseases can be classified into two cat- egories: (1) obstructive (airway) disease, characterized by limitation of airflow, usually resulting from an increase in
resistance caused by partial or complete obstruction at any level, and (2) restrictive disease, characterized by reduced expansion of lung parenchyma accompanied by decreased total lung capacity.
The major diffuse obstructive disorders are emphysema, chronic bronchitis, bronchiectasis, and asthma. In patients with these diseases, forced vital capacity (FVC) is either normal or slightly decreased, while the expiratory flow rate, usually measured as the forced expiratory volume at 1 second (FEV1), is significantly decreased. Thus, the ratio of FEV to FVC is characteristically decreased. Expiratory obstruc- tion may result either from anatomic airway narrowing, classically observed in asthma, or from loss of elastic recoil, characteristic of emphysema.
By contrast, in diffuse restrictive diseases, FVC is reduced and the expiratory flow rate is normal or reduced propor- tionately. Hence, the ratio of FEV to FVC is near normal. The restrictive defect occurs in two general conditions: (1) chest wall disorders in the presence of normal lungs (e.g., with severe obesity, diseases of the pleura, and neuromuscular disor- ders, such as the Guillain-Barré syndrome that affect the respiratory muscles) and (2) acute or chronic interstitial lung diseases. The classic acute restrictive disease is ARDS, discussed earlier. Chronic restrictive diseases include the pneumoconioses, interstitial fibrosis of unknown etiology, and most of the infiltrative conditions (e.g., sarcoidosis).
True
Limit to ehich a baloon can go before it bursts
What are the four disorders in obstructive lung diseases
What are the differences between emphysema and chronic bronchitis
What us the major cause of these two disorders?
What’s the difference between asthma and COPD
These two disorders are clinically grouped together under ehich disease
OBSTRUCTIVE LUNG (AIRWAY) DISEASES In their prototypical forms, the four disorders in this group—emphysema, chronic bronchitis, asthma, and bronchiectasis—have distinct clinical and anatomic charac- teristics but overlaps between emphysema, bronchitis, and asthma are common. At the outset, it should be recognized that the definition of emphysema is morphologic, whereas chronic bronchitis is defined on the basis of clinical features such as the presence of chronic and recurrent cough with excessive mucus secre- tion. Second, the anatomic distribution is partially differ- ent; chronic bronchitis initially involves the large airways, whereas emphysema affects the acinus. In severe or advanced cases of both, small airway disease (chronic bronchiolitis) is characteristic. Although chronic bronchitis may exist without demonstrable emphysema, and almost pure emphysema may occur (particularly in patients with inherited α1-antitrypsin deficiency) (discussed later), the two diseases usually coexist. This is almost certainly because the major cause—cigarette smoking, especially long-term, heavy tobacco exposure—is common to both disorders. In view of their propensity to coexist, emphy- sema and chronic bronchitis often are clinically grouped together under the rubric of chronic obstructive pulmonary disease (COPD).
The primarily irreversible airflow obstruc- tion of COPD distinguishes it from asthma, which, as described later, is characterized largely by reversible airflow obstruction; however, patients with COPD commonly have some degree of reversible obstruction as well
What are the differences between chronic bronchitis,bronchiectasis,asthma,emphysema and bronchiolitis mentioning the clinical entity,the anatomic site,major patjologic changes,causes and signs and symptoms of each entity
Clinical Entity
Anatomic Site
Major Pathologic Changes
Etiology
Signs/Symptoms
Clinical entity: Chronic bronchitis anatomic site:Bronchus
Major pathologic changes:Mucous gland hypertrophy and hyperplasia,
hypersecretion
Causes:Tobacco smoke, air pollutants signs and symptoms:Cough, sputum production
Bronchiectasis:
Site: Bronchus
Major pathological changes:Airway dilation and scarring
Causes:Persistent or severe infections signs and symptoms:Cough, purulent sputum, fever
Asthma
Site:Bronchus
Major pathologic changes:Smooth muscle hypertrophy and hyperplasia, excessive mucus, inflammation
Causes:Immunologic or undefined causes
Signs and symptoms:Episodic wheezing, cough,dyspnea
Emphysema Site:Acinus Changes:Air space enlargement, wall destruction Causes: Tobacco smoke Signs and symptoms:Dyspnea
Small airway disease(bronchiolitis*) Site:Bronchiole Changes:Inflammatory scarring, partial obliteration of bronchioles Causee: Tobacco smoke, air pollutants signs and symptoms :Cough, dyspnea
*Can be present in all forms of obstructive lung disease or by itself.
Emphysema is characterized by what?
Emphysema is classified according to what?
What is a lobule?
What are the four major types of emphysema
Which of the two types cause clinical significant airway obstruction?
Which of the two types is more common
Emphysema is characterized by abnormal permanent enlarge- ment of the air spaces distal to the terminal bronchioles(the acini are are distal to the terminal bronvhioles so structured there are what are affected) accompanied by destruction of their walls without significant fibrosis
Types of Emphysema
Emphysema is classified according to its anatomic distribu- tion 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 (Fig. 12–6, A). There are four major types of emphysema: (1) centriacinar, (2) pan- acinar, (3) distal acinar, and (4) irregular. Only the first two types cause clinically significant airway obstruction, with centriacinar emphysema being about 20 times more common than panacinar disease.
What is the distinctive feature of centriacinar emphysema
Which parts of acini are involved in this type of emphysema
Lesions are more common and severe in which part of the lobes?
In severe centriacinar emphysema what is involved? What does this cause?
This type of emphysema is most commonly seen ad a consequence in ehich group of people?
Ehat is the characteristic of acini in panacinar emphysema ?
Where does this type of emphysema tend to occur?
This type occurs in which disease?
What happens to the acinus in distal acinar emphysema?
Where is this kind of emphysema more striking ?
Where does it occur?
In which area is it more severe?
What is the characteristic finding in this kind of emphysema
What is the range of diameter in air spaces in this kind of emphysema
What are bullae?
Distal acinar emphysema is seen most often in which cases?
What is the characteristic of the acinus in irregular emphysema
What is the most common form of emphysema
The distinctive feature of centriacinar (centrilobular) emphysema is the pattern of involvement of the lobules: The central or proximal parts of the acini, formed by respiratory bronchioles, are affected, while distal alveoli are spared. Thus, both emphysematous and normal air spaces exist within the same acinus and lobule (Fig. 12–6, B). The lesions are more common and severe in the upper lobes, particularly in the apical segments. In severe centriacinar emphysema the distal acinus also becomes involved, and thus, the dif- ferentiation from panacinar emphysema becomes difficult. This type of emphysema is most commonly seen as a con- sequence of cigarette smoking in people who do not have congenital deficiency of α1-antitrypsin.
Panacinar (Panlobular) Emphysema In panacinar (panlobular) emphysema, the acini are uniformly enlarged, from the level of the respiratory bronchiole to the terminal blind alveoli (Fig. 12–6, C). In contrast with centriacinar emphysema, panacinar emphysema tends to occur more commonly in the lower lung zones and is the type of emphysema that occurs in α1-antitrypsin deficiency.
Distal Acinar (Paraseptal) Emphysema In distal acinar (paraseptal) emphysema, the proximal portion of the acinus is normal but the distal part is primarily 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, scar- ring, or atelectasis and is usually more severe in the upper half of the lungs. The characteristic finding is the presence of multiple, contiguous, enlarged air spaces ranging in diameter from less than 0.5 mm to more than 2.0 cm, some- times forming cystic structures that, with progressive enlargement, are referred to as bullae. The cause of this type of emphysema is unknown; it is seen most often in cases of spontaneous pneumothorax in young adults.
Irregular Emphysema
Irregular emphysema, so named because the acinus is irregularly involved, is almost invariably associated with scarring, such as that resulting from healed inflammatory diseases. Although clinically asymptomatic, this may be the most common form of emphysema.
What is the pathogenesis of emphysema (what induced inflammation? What causes epithelial injury and proteolysis if thr ECM?
Give an example of an antielestase
Which people mostly develop symptomatic panacinar emphysema? And when does it occur? After smoking,ehich other factor controls response to injury and how does it cause Emphysema? Which matrix metalloproteinases have a pathogenic role in emphysema and how do they work?
What results result in different diseases? Name the diseases they resilt in?
Why can emphysema be thought of as resulting from insufficient wound repair?
What causes unchecked scarring un patients with fibrosing lung diseases?
Exposure to toxic substances such as tobacco smoke and inhaled pollutants induces ongoing inflammation with accu- mulation of neutrophils, macrophages and lymphocytes in the lung. Elastases, cytokines (including IL-8) and oxidants are released causing epithelial injury and proteolysis of the extra- cellular matrix (ECM). Elastin degradation products further increase the inflammation. Unless checked by antielastases
(e.g., α1-antitrypsin) and antioxidants, the cycle of inflamma- tion and ECM proteolysis continues.
Indeed, more than 80% of patients with congenital α1-antitrypsin deficiency develop symptomatic panacinar emphysema, which occurs at an earlier age and with greater severity if the affected person smokes.
Multiple genetic factors control the response to injury after smoking. For example, the TGFB gene exhibits polymorphisms that influence suscep- tibility to the development of COPD by regulating the response of mesenchymal cells to injury. For example, with certain polymorphisms, mesenchymal cell response to TGF-β signaling is reduced, which in turn results in inadequate repair of elastin injury caused by inhaled toxins.
Matrix metallopro- teinases (MMPs), especially MMP-9 and MMP-12, have also been shown to have a pathogenic role in emphysema. MMP-9 gene polymorphisms and higher levels of both MMP-9 and MMP-12 have been found in some emphysema patients. Moreover, MMP-12–deficient mice are protected from ciga- rette smoke–induced emphysema.
Complex interactions between inflammatory mediators, cell signaling and inappropriate activation of repair mecha- nisms may result in very different diseases: tissue destruction without fibrosis (emphysema) or interstitial fibrosis
Recent data indicate that mesenchymal cell response may be a key factor in determining which of these two processes ensues. In emphysema there is loss of not only epithelial and endothelial cells but also mesenchymal cells, leading to lack of extracellular matrix, the scaffolding upon which epithelial cells would have grown. Thus, emphysema can be thought of as resulting from insufficient wound repair. By contrast, patients with fibrosing lung dis- eases have excessive myofibroblastic or fibroblastic response to injury, leading to unchecked scarring.
Diagnosis and classification of emphysema depend largely on what?
What is the gross morphology of panacinar emphysema when its well developed?
What are the macroscopic features of centriacinar emphysema
Which part of the lungs are severely affected in centriacinar emphysema
Histologic exam in this kind of emphysema reveals what?
Why will terminal and respiratory bronchioles be deformed ?
What will cause small airway collapse during expiration
What two things are consistently present in advanced disease?
What are the features of pulmonary emphysema
MORPHOLOGY
The diagnosis and classification of emphysema depend largely on the macroscopic appearance of the lung. Panacinar emphysema, when the pathologic process is well devel- oped, produces pale, voluminous lungs that often obscure the heart when the anterior chest wall is removed at autopsy. The macroscopic features of centriacinar emphysema are less impressive. The lungs are a deeper pink than in pan- acinar emphysema and less voluminous, unless the disease is well advanced. Generally, in centriacinar emphysema the upper two thirds of the lungs are more severely affected than the lower lungs. Histologic examination reveals destruction of alveolar walls without fibrosis, leading to enlarged air spaces In addition to alveolar loss, the number of alveolar capillaries is diminished. Terminal and respiratory bronchioles may be deformed because of the loss of septa that help tether these structures in the parenchyma. With the loss of elastic tissue in the surrounding alveolar septa, radial traction on the small airways is reduced. As a result, they tend to collapse during expiration—an important cause of chronic airflow obstruction in severe emphysema. Bronchiolar inflammation and submucosal fibrosis are consis- tently present in advanced disease.
Pulmonary emphysema. There is marked enlargement of air spaces, with destruction of alveolar septa but without fibrosis. Note presence of black anthracotic pigment
What is the first symptom in emphysema? And whats the character of the symptom or duration
Cough and wheezing may be initial complaints in which patients?
When will weight loss be severe in emphysema?
What test will be done?
What does this test reveal?
What does this mean for the ratio of FEV1 to FVC
What is the classic presentation in emphysema with no bronchitic component?
In patients w this disease,air space enlargement is severe and diffusing capacity is low true or false?
Which two signs are prominent so that until very late in the disease what happens to gas exchange?
Why are these patients called pink puffers?
At the other extreme of the clinical presentation in emphysema is a patient who also has pronounced chronic bronchitis and a history of recurrent infections with puru- lent sputum,state the clinical features in such a person
Why are such people called blue bloaters?
When do they seek medical help?
In all cases secondary pulmonary hypertension develops gradually arising from where?
Death from emphysema is related to what four signs?
Clinical Features
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. Pulmonary function tests reveal reduced FEV1 with normal or near-normal FVC. Hence, the ratio of FEV1 to FVC is reduced.
The classic presentation in emphysema with no “bron- chitic” component is one in which the patient is barrel- chested and dyspneic, with obviously prolonged expiration, sitting forward in a hunched-over position, attempting to squeeze the air out of the lungs with each expiratory effort. In these patients, air space enlargement is severe and dif- fusing capacity is low. Dyspnea and hyperventilation are prominent, so that until very late in the disease, gas exchange is adequate and blood gas values are relatively normal. Because of prominent dyspnea and adequate oxy- genation of hemoglobin, these patients sometimes are called “pink puffers.”
At the other extreme of the clinical presentation in emphysema is a patient who also has pronounced chronic bronchitis and a history of recurrent infections with puru- lent sputum. Dyspnea usually is less prominent, with diminished respiratory drive, so the patient retains carbon dioxide, becomes hypoxic, and often is cyanotic.
For reasons not entirely clear, such patients tend to be obese— hence the designation “blue bloaters.” Often they seek medical help after the onset of CHF (cor pulmonale) (Chapter 10) and associated edema.
Most patients with emphysema and COPD, however, fall somewhere between these two classic extremes. In all cases, secondary pulmonary hypertension develops gradu- ally, arising from both hypoxia-induced pulmonary vascu- lar spasm and loss of pulmonary capillary surface area from alveolar destruction. Death from emphysema is related to either pulmonary failure, with respiratory acido- sis, hypoxia, and coma, or right-sided heart failure (cor pulmonale).
Summarize emphysema (What is it? What are the subtypes? In which people are these types seen? Smoking and inhaled pollutants cause what? And what do they lead to? Most patients w emphysema demonstrate elements of chronic bronchitis concurrently Why? Patients w pure emphysema are characterized as what?)
What us compensatory emphysema?
What is obstructive overinflation?
What is a common cause of obstructive overinflation?
What is bullous emphysema ?
What do yhe blebs in this kind of emphysema represent?
When they rupture what do they lead to?
What is mediastinal emphysema
When does it occur? And what does it result in?
Sometimes it develops in ehich group of people?
It is particularly likely to occur in which groups of patients?
What will make the patient blow up like a balloon,with marked swelling of the head and neck and crackling crepitation all over the chest?
Emphysema
• Emphysema is a chronic obstructive airway disease char- acterized 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 accumula- tion of inflammatory cells, releasing elastases and oxidants, which destroy the alveolar walls without adequate mes- enchymal 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.”
Conditions Related to Emphysema
Several conditions resemble emphysema only superfi- cially but nevertheless are (inappropriately) referred to as such:
• Compensatory emphysema is a term used to designate the compensatory dilation of alveoli in response to loss of lung substance elsewhere, such as occurs in residual lung parenchyma after surgical removal of a diseased lung or lobe.
• Obstructive overinflation refers to the condition in which the lung expands because air is trapped within it. A common cause is subtotal obstruction by a tumor or foreign object. Obstructive overinflation can be a life-threatening emergency if the affected portion extends sufficiently to compress the remaining normal lung.
• Bullous emphysema refers merely to any form of emphy- sema that produces large subpleural blebs or bullae (spaces greater than 1 cm in diameter in the distended state) (Fig. 12–9). Such blebs represent localized accen- tuations of one of the four forms of emphysema; most often the blebs are subpleural, and on occasion they may rupture, leading to pneumothorax.
• Mediastinal(interstitial) emphysema is the condition result- ing when air enters the connective tissue stroma of the lung, mediastinum, and subcutaneous tissue. This may occur spontaneously with a sudden increase in intra- alveolar pressure (as with vomiting or violent coughing) resulting in a tear, with dissection of air into the inter- stitium. Sometimes it develops in children with whoop- ing cough. It is particularly likely to occur in patients on respirators who have partial bronchiolar obstruction or in persons who suffer a perforating injury (e.g., a frac- tured rib). When the interstitial air enters the subcutane- ous tissue, the patient may literally blow up like a balloon, with marked swelling of the head and neck and crackling crepitation all over the chest. In most instances, the air is resorbed spontaneously after the site of entry is sealed.
chronic bronchitis is common among which people?
Diagnosis of chronic bronchitis is made on ehat grounds?
What is chronic bronchitis?
In early stages of the disease what sign is seen?
Some patients w vhronic bromchitis may demonstrate what?
Which bronchitic patients develop chronic outflow obstruction associated w emphysema?
What are the clinical features of patients e chronic bronchitis?
What 3 signs are seen in chronic bronchitis pateints in ehich the disease develops into significant COPD w outflow obstruction ?
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
True or false .
With progression,Chronic bronchitus is complicated by what two diseases ?
Which two diseases are constant threats?
Chronic bronchitis is common among cigarette smokers and urban dwellers in smog-ridden cities;
The diagnosis of chronic bron- chitis is made on clinical grounds: it is defined by the pres- ence 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 hyperresponsive airways with intermittent bronchospasm and wheezing. A subset of bronchitic patients, especially heavy smokers, develop chronic outflow obstruction, usually with associated emphysema.
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”).
With progression, chronic bronchitis is compli- cated by pulmonary hypertension and cardiac failure (Chapter 10). Recurrent infections and respiratory failure are constant threats.
What is the distinctive feature of chronic bronchitis and where does it begin?
Name two other air pollutants that may contribute to this disease?
How do these environmental irritants cause chronic bronchitis?
Whats the difference between bronchitis and asthma ?
What is the defining feature of chronic bronchitis?
The morphological basis of airflow obstruction in chronic bronchitis results from which teo diseases?
What induces the small airway disease?
chronic bronchitis with significant airflow obstruction is almost always complicated by emphysema true or false?
Many of the respiratory epithelial effects of environmental irritants (e.g., mucus hypersecre- tion) are mediated by local release of which substances?
What teo things are increased as a consequence of exposire to tobacco smoke?
Microbial infection is often present . What is its secondary role
What is the gross appearance of the mucosal lining pf the larger airways?
It is foten covered w what?
On histologic exam whats the diagnostic feature of chronic bronchitis in the trachea and larger bronchi?
How is the magnitude of the increase in size assessed? What is the normal Reid index?
What is the appearance of inflammatory cells? Chronic bronchiolitis is characterized by what four things?
In most severe cases what may be seen ? What leads to luminal narrowingand airway obstruction
The distinctive feature of chronic bronchitis is hypersecre- tion of mucus, beginning in the large airways. Although the single most important cause is cigarette smoking, other air pollutants, such as sulfur dioxide and nitrogen dioxide, may contribute. These environmental irritants induce hypertro- phy of mucous glands in the trachea and main bronchi, leading to a marked increase in mucin-secreting goblet cells in the surface epithelium of smaller bronchi and bronchioles. In addition, these irritants cause inflammation with infiltration of CD8+ lymphocytes, macrophages, and neutrophils. In contrast with asthma, there are no eosinophils in chronic bronchitis. Whereas the defining feature of chronic bronchitis (mucus hypersecretion) is primarily a reflection of large bron- chial involvement, 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 bronchio- lar lumen, inflammation, and bronchiolar wall fibrosis, and (2) coexistent emphysema. In general, while small airway disease (also known as chronic bronchiolitis) is an important component of early and relatively mild airflow obstruction,.
It is postulated that many of the respiratory epithelial effects of environmental irritants (e.g., mucus hypersecre- tion) are mediated by local release of T cell cytokines such as IL-13. The transcription of the mucin gene MUC5AC in bronchial epithelium and the production of neutrophil elas- tase are increased as a consequence of exposure to tobacco smoke. Microbial infection often is present but has a sec- ondary role, chiefly by maintaining the inflammation and exac- erbating symptoms.
As seen in gross specimens, the mucosal lining of the larger airways usually is hyperemic and swollen by edema fluid. It often is covered by a layer of mucinous or mucopurulent secretions. The smaller bronchi and bronchioles also may be filled with similar secretions. On histologic examination, the diagnostic feature of chronic bronchitis in the trachea and larger bronchi is enlargement of the mucus-secreting glands (Fig. 12–10). The magnitude of the increase in size is assessed by the ratio of the thickness of the submucosal gland layer to that of the bronchial wall (the Reid index— normally 0.4). Inflammatory cells, largely mononuclear but sometimes admixed with neutrophils, are frequently present in variable density in the bronchial mucosa. Chronic bron- chiolitis (small airway disease), characterized by goblet cell metaplasia, mucous plugging, inflammation, and fibrosis, is also present. In the most severe cases, there may be com- plete obliteration of the lumen as a consequence of fibrosis (bronchiolitis obliterans). It is the submucosal fibrosis that leads to luminal narrowing and airway obstruction. Changes of emphysema often co-exist.
Summarize chronic bronchitis(what is it? Whats the most common underlining risk factor?
Chronic obstructive component largely results from what? Histologic exam demonstrates what three things)
What is asthma?
What are the six hallmarks of asthma?
Some of the stimuli that trigger attacks in patients would have little or no effect in persons with normal airways
True or false
Which 6 cells play a role in the inflammatory response in asthma?.
Asthma may be categorized into ehich two groups?
In atopic asthma,there’s evidence of allergen sensitization often in which group of patients?
In both types of asthma,episodes of bronchospasm can be triggered by what 5 mechanisms?
There is emerging evidence for differing patterns of inflammation: eosinophilic, neu- trophilic, mixed inflammatory, and pauci-granulocytic. These subgroups may differ in etiology, immunopathol- ogy, and response to treatment. Asthma also may be classified according to the agents or events that trigger bronchoconstriction.
True or false
Chronic Bronchitis
• Chronic bronchitis is defined as persistent productive cough for at least 3 consecutive months in at least 2 consecutive years.
• Cigarette smoking is the most important underlying risk factor; air pollutants also contribute.
Chronic obstructive component largely results from small airway disease (chronic bronchiolitis) and coexistent emphysema.
• Histologic examination demonstrates enlargement of mucus-secreting glands, goblet cell metaplasia, and bron- chiolar wall fibrosis.
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 inflammation with eosinophils, bronchial smooth muscle cell hypertrophy and hyperreactivity, and increased mucus secretion.
Many cells play a role in the inflammatory response, in particular eosinophils, mast cells, macrophages, lympho- cytes, neutrophils, and epithelial cells.
Asthma may be categorized into atopic (evidence of allergen sensitization, often in a patient with a history of allergic rhinitis, eczema) and nonatopic. In either type, epi- sodes of bronchospasm can be triggered by diverse mecha- nisms, such as respiratory infections (especially viral), environmental exposure to irritants (e.g., smoke, fumes), cold air, stress, and exercise.
Whag are the 4 major etiologic factors of asthma?
The role of which type of cells may be critical to the pathogenesis of asthma?
Classic atopic form of asthma is associated w what?
Cytokines produced by TH2 cells account for most of the features of asthma . Name the cytokines produced by those cells and their functions in asthma
How does IgE play a role in asthma?
Which teo waves of reaction are induced when granule contents are released?
The early reaction is dominated by what three things?
What triggers bronchoconstriction
What does the late phase reaction consist of ? Which cells are activated in this phase?
What happens when epithelial cellsa re activated? Repeated bouts of inflammation lead to what? What changed are seen in airway remodeling
Asthma is a complex genetic disorder in which multiple susceptibility genes interact with environmental factors to initiate the pathologic reaction. There is significant variation in the expression of these genes and in the combinations of polymorphisms that effect the immune response or tissue remodeling. One of the susceptibility loci is on the long arm of chromosome 5 (5q), where several genes involved in regu- lation of IgE synthesis and mast cell and eosinophil growth and differentiation map. The genes at this locus include IL13 (genetic polymorphisms linked with susceptibility to the development of atopic asthma), CD14 (single-nucleotide polymorphisms associated with occupational asthma), class II HLA alleles (tendency to produce IgE antibodies), β2- adrenergic receptor gene, and IL-4 receptor gene (atopy, total serum IgE level, and asthma). Another important locus is on 20q where ADAM-33 that regulates proliferation of bronchial smooth muscle and fibroblasts is located; this con- trols airway remodeling. Upregulation of various chitinase enzymes has been shown to be important in TH2 inflamma- tion and severity of asthma; high serum YKL-40 levels (a chitinase family member with no enzymatic activity) correlate with the severity of asthma. True or false
PATHOGENESIS
The major etiologic factors of asthma are genetic predisposi- tion to type I hypersensitivity (atopy), acute and chronic airway inflammation, and bronchial hyperresponsiveness to a variety of stimuli. The inflammation involves many cell types and numerous inflammatory mediators, but the role of type 2 helper T (TH2) cells may be critical to the pathogenesis of asthma. The classic atopic form of asthma is associated with an excessive TH2 reaction against environmental antigens. Cytokines produced by TH2 cells account for most of the features of asthma—IL-4 stimulates IgE production, IL-5 activates eosinophils, and IL-13 stimu- lates mucus production and also promotes IgE production by B cells.
IgE coats submucosal mast cells, which, on exposure to allergen, release granule contents. This induces two waves of reaction: an early (immediate) phase and a late phase (Fig. 12-11). The early reaction is dominated by bronchoconstric- tion, increased mucus production and variable vasodilation. Bronchoconstriction is triggered by direct stimulation of sub- epithelial vagal receptors. The late-phase reaction consists of inflammation, with activation of eosinophils, neutrophils, and T cells. In addition, epithelial cells are activated to produce chemokines that promote recruitment of more TH2 cells and eosinophils (including eotaxin, a potent chemoattractant and activator of eosinophils), as well as other leukocytes, thus amplifying the inflammatory reaction. Repeated bouts of inflammation lead to structural changes in the bronchial wall, collectively referred to as airway remodeling. These changes include hypertrophy of bronchial smooth muscle and mucus glands, and increased vascularity and deposition of subepithelial collagen, which may occur as early as several years before initiation of symptoms.
What are the two main types of asthma
Which type is most common and when does it usually occur ?
A positive family history of atopy and or asthma is common and asthmatic attacks are often preceded by ehat three things?
What two main things trigger the immune type of asthma?
What two tests can diagnose Immune type of asthma?
In which type of asthma do patients dont have evudence of allergic sensitization,skin test negative and a positive fam history of asthma is less common?
What are the common triggers of this type of asthma?
What is the pathogenesis of this type of asthma?
State two other types of asthma and explain how they develop and what triggers them
Types of Asthma
Atopic Asthma
This is the most common type of asthma, usually beginning in childhood, and is a classic example of type I IgE–mediated hypersensitivity reaction (Chapter 4).
A positive family history of atopy and/or asthma is common, and asthmatic attacks are often preceded by allergic rhinitis, urticaria, or eczema. The disease is triggered by environmental anti- gens, such as dusts, pollen, animal dander, and foods. Infections can also trigger atopic asthma. A skin test with the offending antigen results in an immediate wheal-and- flare reaction. Atopic asthma also can be diagnosed based on serum radioallergosorbent tests (RASTs) that identify the presence of IgE specific for a panel of allergens.
Non-Atopic Asthma
Patients with nonatopic forms of asthma do not have evi- dence of allergen sensitization, and skin test results usually are negative. A positive family history of asthma is less common. Respiratory infections due to viruses (e.g., rhino- virus, parainfluenza virus) and inhaled air pollutants (e.g., sulfur dioxide, ozone, nitrogen dioxide) are common trig- gers. It is thought that virus-induced inflammation of the
respiratory mucosa lowers the threshold of the subepithelial vagal receptors to irritants. Although the connections are not well understood, the ultimate humoral and cellular mediators of airway obstruction (e.g., eosinophils) are common to both atopic and nonatopic variants of asthma, so they are treated in a similar way.
Drug-Induced Asthma
Several pharmacologic agents provoke asthma, aspirin being the most striking example. Patients with aspirin sensitivity present with recurrent rhinitis and nasal polyps, urticaria, and bronchospasm. The precise mecha- nism remains unknown, but it is presumed that aspirin inhibits the cyclooxygenase pathway of arachidonic acid metabolism without affecting the lipoxygenase route, thereby shifting the balance of production toward leuko- trienes that cause bronchial spasm.
Occupational Asthma
This form of asthma is stimulated by fumes (epoxy resins, plastics), organic and chemical dusts (wood, cotton, plati- num), gases (toluene), and other chemicals. Asthma attacks usually develop after repeated exposure to the inciting antigen(s).
What happens in the triggering of asthma (C)
Just read through the answer
Its bene covered
But the early ohase takes minutes and the late phase takes hours
Summarize asthma( what its charcaterized by, what causes atopic asthma and what characterizes it, which cytokines are imoortant mediators in atopic asthma,triggers for non atopic asthma? Which cells are key inflammatory cells found in all subtypes of asthma? Which productd are responsibie for airway damage? What adds an irreversible compenent to the obstructive disease?
A and B, Comparison of a normal bronchus with that in a patient with asthma. Note the accumulation of mucus in the bronchial lumen resulting from an increase in the number of mucus-secreting goblet cells in the mucosa and hypertrophy of submucosal glands. In addition, there is intense chronic inflammation due to recruitment of eosinophils, macrophages, and other inflammatory cells. Basement membrane underlying the mucosal epithelium is thickened, and smooth muscle cells exhibit hypertrophy and hyperplasia. C, Inhaled allergens (antigens) elicit a TH2-dominated response favoring IgE production and eosinophil recruitment (priming or sensitization). D, On reexposure to antigen (Ag), the immediate reaction is triggered by antigen-induced cross-linking of IgE bound to IgE receptors on mast cells in the airways. These cells release preformed mediators. Col- lectively, either directly or through neuronal reflexes, the mediators induce bronchospasm, increase vascular permeability and mucus production, and recruit additional mediator-releasing cells from the blood. E, The arrival of recruited leukocytes (neutrophils, eosinophils, basophils, lymphocytes, and monocytes) signals the initiation of the late phase of asthma and a fresh round of mediator release from leukocytes, endothelium, and epithelial cells. Factors, particularly from eosinophils (e.g., major basic protein, eosinophil cationic protein), also cause damage to the epithelium. IgE, immuno- globulin E.
SUMMARY
Asthma
• Asthma is characterized by reversible bronchoconstric- tion caused by airway hyperresponsiveness to a variety of stimuli.
• 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. The TH2 cytokines IL-4, IL-5, and IL-13 are important mediators.
• Triggers for nonatopic asthma are less clear but include viral infections and inhaled air pollutants, which can also trigger atopic asthma.
• Eosinophils are key inflammatory 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.
Morphologic changes in asthma have been described in which persons?
In gross specimens obstained in fatal cases what is the appearance of the lung? What is the most striking macroscopic finding in asthma?
Histologically what are the two things seen (the mucous plugs in asthma contain what? What else are present? What are Charcot-Leyden crystals? )
What are the airway remodeling morpholgic changes jn asthma?
An attack of asthma is characterized by which sign? Chief difficukty lies in what? When victim labors to get aur into the lungs and cant get ut out what hapoens to the lungs and bronchi?
In the usual case how long do the attacks last and how do they subside?
Whats the hse of spirometry in asthma?
What is status asthmaticus?
What are the three signs associated with it?
The morphologic changes in asthma have been described in persons who die of prolonged severe attacks (status asth- maticus) and in mucosal biopsy specimens of persons chal- lenged with allergens.
In gross specimens obtained in fatal cases, the lungs are overdistended because of overinflation, and there may be small areas of atelectasis.
The most striking macroscopic finding is occlusion of bronchi and bronchioles by thick, tenacious mucous plugs.
Histologically, the mucous plugs contain whorls of shed epithelium (Cursch- mann spirals). Numerous eosinophils and Charcot- Leyden crystals (collections of crystalloids made up of eosinophil proteins) also are present. Other characteristic morphologic changes in asthma, collectively called “airway remodeling,” include (Fig. 12–11, B):
• Thickening of airway wall
• Sub-basement membrane fibrosis (Fig. 12–12)
• Increased vascularity in submucosa
• An increase in size of the submucosal glands and goblet
cell metaplasia of the airway epithelium
• Hypertrophy and/or hyperplasia of the bronchial muscle
(this is the basis for the novel therapy of bronchial thermoplasty, which involves controlled delivery of thermal energy during bronchoscopy; this reduces the mass of smooth muscles which in turn reduces airway hyperresponsiveness)
Clinical Features An attack of asthma is characterized by severe dyspnea with wheezing; the chief difficulty 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 filled 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
. Intervals between attacks are charac- teristically free from overt respiratory difficulties, but persistent, subtle deficits can be detected by spirometry. Occasionally a severe paroxysm occurs that does not respond to therapy and persists for days and even weeks (status asthmaticus). The associated hypercapnia, acidosis, and severe hypoxia may be fatal, although in most cases the condition is more disabling than lethal.
What is bronchiectasis
Bronciectasis is a primary disease true or false?
Once bronchiectasis is developed,it gives rise to a charcateristic symtom complex dominated by what signs?
Diagnosis depends on what?
What conditions most commonly predispose one to bronchiectasis? And state their causes and what thise conditons are.
Bronchiectasis can complicate what?
Name and explain three congenital or hereditaty conditions that predispose one to 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.
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 dila- tion. The conditions that most commonly predispose to bronchiectasis include: • Bronchial obstruction:.Commoncausesaretumors,foreign bodies, and occasionally impaction of mucus. With these conditions, the bronchiectasis is localized to the obstructed lung segment. Bronchiectasis can also com- plicate atopic asthma and chronic bronchitis. • Congenital or hereditary conditions—for example: In cystic fibrosis, widespread severe bronchiectasis results from obstruction caused by the secretion of abnormally viscid mucus thus predisposing to infec- tions of the bronchial tree. This is an important and serious complication (Chapter 6). In immunodeficiency states, particularly immunoglobu- lin deficiencies, localized or diffuse bronchiectasis is likely to develop because of an increased susceptibil- ity to repeated bacterial infections. Kartagener syndrome is a rare autosomal recessive disorder that is frequently associated with bron- chiectasis and with sterility in males. In this condi- tion, structural abnormalities of the cilia impair mucociliary clearance in the airways, leading to per- sistent infections, and reduce the mobility of spermatozoa . • Necrotizing, or suppurative, pneumonia, particularly with virulent organisms such as Staphylococcus aureus or Klebsiella spp., may predispose affected patients to development of bronchiectasis. Posttuberculosis bron- chiectasis continues to be a significant cause of morbid- ity in endemic areas.
What is the pathogenesis of bronchiectasis(state the two processes crucial and intertwined in the pathogenesis of bronchiectasis?
Explain how these processes cause bronciectasis and give an example
What are the clincial manifestations of bronchiectasis?
What mag sputum in bronchiectasis contain?
What is the tkming of the symptomsand what precipitates them
In cases of severe widespread bronchiectasis,what is usual and what four diseases are seen?
Name two less frequent complications of bronchiectasis
Bronchiectasis usually affects which parts of the lobes?
When this dusease is caused by tumors or aspiration of foreign bodies what can happen?
The msot severe involvement is found where?
The airways may be dilated by how
Many times their usualy diameter?
In normal lungs bronchioles cant be followed by ordinary gross exam beyond which point?
Histologic findings vary w what two things?
In a full blown active case,what causes extensive areas of ulceration?
In yhe usual cade ehich flora can be cultured from the involved bronchi?
Which are particular in kids?
When healing occurs what happens to the lining of the epithelium?
What develops in more chronic cases?
In some cases what causes a fungus ball to develop?
Two processes are crucial and intertwined in the pathogen- esis of bronchiectasis: obstruction and chronic persis- tent infection. Either of these may come first. Normal clearance mechanisms are hampered by obstruction, so sec- ondary infection soon follows; conversely, chronic infection over time causes damage to bronchial walls, leading to weak- ening and dilation. For example, obstruction caused by a primary lung cancer or a foreign body impairs clearance of secretions, providing a favorable substrate for superim- posed infection. The resultant inflammatory damage to the bronchial wall and the accumulating exudate further distend the airways, leading to irreversible dilation. Conversely, a persistent necrotizing inflammation in the bronchi or bron- chioles may cause obstructive secretions, inflammation throughout the wall (with peribronchial fibrosis and traction on the walls), and eventually the train of events already described.
Clinical Features
The clinical manifestations consist of severe, persistent cough with expectoration of mucopurulent, sometimes fetid, sputum. The sputum may contain flecks of blood; frank hemoptysis can occur. Symptoms often are episodic and are precipitated by upper respiratory tract infections or the introduction of new pathogenic agents. Clubbing of the fingers may develop.
In cases of severe, widespread bronchiectasis, significant obstructive ventilatory defects are usual, with hypoxemia, hypercapnia, pulmonary hypertension, and (rarely) cor pulmonale.
Metastatic brain abscesses and reactive amyloidosis are other, less frequent complications of bronchiectasis.
Morphology:
Bronchiectasis usually affects the lower lobes bilaterally, particularly those air passages that are most vertical. When caused by tumors or aspiration of foreign bodies the involve- ment may be sharply localized to a single segment of the lungs.
Usually, the most severe involvement is found in the more distal bronchi and bronchioles. The airways may be dilated to as much as four times their usual diameter and on gross examination of the lung can be followed almost to the pleural surfaces
By contrast, in normal lungs, the bronchioles cannot be followed by ordinary gross exami- nation beyond a point 2 to 3 cm from the pleural surfaces.
The histologic findings vary with the activity and chronicity of the disease. In the full-blown active case, 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.
In the usual case, a mixed flora can be cultured from the involved bronchi, including staphylococci, streptococci, pneumococci, enteric organisms, anaerobic and microaerophilic bacteria, and (particularly in children) Haemophilus influenzae and Pseu- domonas aeruginosa.
When healing occurs, the lining epithe- lium may regenerate completely; however, usually so much injury has occurred that abnormal dilation and scarring persist.
Fibrosis of the bronchial and bronchiolar walls and peribronchiolar fibrosis develop in more chronic cases. In some instances, the necrosis destroys the bronchial or bronchiolar walls resulting in the formation of an abscess cavity within which a fungus ball may develop.
What does chest X ray show for acute respiratory distress syndrome and what does it signify in the case of ARDS
Ground-glass opacification on CT is a non-specific sign that reflects an overall reduction in the air content of the affected lung. In the case of acute ARDS, this is likely to represent edema and protein within the interstitium and alveoli
The alveolar are made up of two different thoes of cells name them and stte their functions
➢Type I pneumocytes. These are the cells responsible for the exchange of oxygen and CO2
➢Type II pneumocytes. These cells perform two important functions. They produce surfactant, which helps keep the balloon shape from collapsing. They can also turn into type I cells in order to repair damage
•They also contain immune cells called alveolar macrophages. Macrophages are like the garbage trucks of the immune system. These cells phagocytize, or eat debris.
- .
- .
What are chronic interstitial diseases
What is the pulmonary interstitium comprised of?
Many of the entities in this group are of unknown cause and pathogenesis; some have an intra-alveolar as well as an interstitial component, and there is frequent overlap in his- tologic features among the different conditions. Neverthe- less, the similarity in clinical signs, symptoms, radiographic alterations, and pathophysiologic changes justifies their consideration as a group.
True or false
What is the hallmark feature of chronic interstitial diseases? And explain what it is and what it leads to
What causes hypoxia in this group of diseases
What does chest radiograph show?
With progression,patients can develop what? Often in association with which two diseases?
Why will sdvanced forms of chronic interstitial diseases be hard to differentiate?
What is honeycomb lung?
How are chronic interstitial lung diseases categorized?
CHRONIC INTERSTITIAL (RESTRICTIVE, INFILTRATIVE) LUNG DISEASES Chronic interstitial diseases are a heterogeneous group of disorders characterized predominantly by bilateral, often patchy, and usually chronic involvement of the pulmonary connective tissue, principally the most peripheral and deli- cate interstitium in the alveolar walls. The pulmonary interstitium is composed of the basement membrane of the endothelial and epithelial cells (fused in the thinnest por- tions), collagen fibers, elastic tissue, fibroblasts, a few mast cells, and occasional mononuclear cells .
The hallmark feature of these disor- ders is reduced compliance (i.e., more pressure is required to expand the lungs because they are stiff), which in turn necessi- tates increased effort of breathing (dyspnea).
Furthermore, damage to the alveolar epithelium and interstitial vascula- ture produces abnormalities in the ventilation–perfusion ratio, leading to hypoxia.
Chest radiographs show diffuse infiltration by small nodules, irregular lines, or “ground- glass shadows.”
With progression, patients can develop respiratory failure, often in association with pulmonary hypertension and cor pulmonale (Chapter 10).
Advanced forms of these diseases may be difficult to differentiate because they result in scarring and gross destruction of the lung, referred to as end-stage or “honeycomb” lung. Chronic interstitial lung diseases are categorized based on clinicopathologic features and characteristic histology
What is idiopathic pulmonary fibrosis
What is it also known as?
What is it characterized by?
Which gender is more affected?
The radiologic and histologic pattern of fibrosis is referred to as what?
What is required for diagnosis if idiopathic pulmonary fibrosis
There are similar pathologic changes in yhe lung which may be present in other diseases,therefore known causes must be ruled out before the appellation of idiopathic is used.
Name two of those other diseases
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF), also known as crypto- genic fibrosing alveolitis, refers to a pulmonary disorder of unknown etiology. It is characterized by patchy but pro- gressive bilateral interstitial fibrosis, which in advanced cases results in severe hypoxemia and cyanosis. Males are affected more often than females, and approximately two thirds of patients are older than 60 years of age at presenta- tion.
The radiologic and histologic pattern of fibrosis is referred to as usual interstitial pneumonia (UIP), which is required for the diagnosis of IPF.
Of note, however, similar pathologic changes in the lung may be present in well- defined entities such as asbestosis, the collagen vascular diseases, and a number of other conditions. Therefore, known causes must be ruled out before the appellation of idiopathic is used.
