Path Respiratory System I (15)

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Path Respiratory System I (15)
2014-03-02 17:46:54
MBS Pathology
Exam 3
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  1. What do the primary lung disease affect?
    • 1. the airways
    • 2. the interstitium (especially in the wall of the alveoli)
    • 3. the pulmonary vascular system (artery/vein/capillary network)
  2. Atelectasis (Pulmonary Collapse)
    • collapse or closure of the lung resulting in reduced or absent gas exchange
    • loss of lung volume caused by inadequate expansion of airspaces (from alveoli collapse in adults or incomplete expansion of the alveoli in neonates)
    • results in the shunting of inadequately oxygenated blood from pulmonary artery to veins → ventilation-perfusion imbalance & hypoxia
    • is reversible & treatment helps prevent hypoxemia & superimposed infection of the collapsed lung
  3. Resorption Atelectasis
    • collapse of the alveoli distal to an obstructed airway
    • b/c of the obstruction the air already present in the distal area gradually becomes absorbed, preceding alveolar collapse
    • an entire lung, lobe, or one or more segments may be involved depending on how far down an object travels before forming an obstruction
    • "air is used up"
  4. What is the most common cause of resorption atelectasis?
    • mucous or mucopurulent (puss-like) plugs like those seen in patients with asthma or following surgery
    • can also be caused by tumors, complications of bronchiectasis or chronic bronchitis, & aspiration of foreign bodies (esp. in children)
  5. Compression (Passive or Relaxation) Atelectasis
    • mechanical collapse of alveoli is caused by external pressure
    • caused by accumulation of fluid (eg. pleural effusion from CHF), blood (hemothorax), or air (pneumothorax) within the pleural cavity; also by a neoplasm
    • may be reversible if fluid can be removed (suck fluid out using chest tube)
    • "air is squeezed out due to pressure"
  6. Which side has the pneumothorax?
    • the left side
  7. Basal Atelectasis
    a type of compression atelectasis that results from the diaphragm being abnormally & consistently elevated (commonly occurs in patients who are bedridden, have ascites, & during/after surgery due to a positional effect)
  8. Hemothorax
    • a form of compression atelectasis
    • a condition that results from blood accumulating in the pleural cavity
    • cause is usually traumatic & results in a rupture of the serous membrane either lining the thorax or covering the lungs → blood spilling into the pleural space
  9. Contraction Atelectasis (Cicatrization)
    • occurs when local or generalized fibrotic changes in the lung or pleura make full expansion not possible
    • additionally, it causes an increase in elastic recoil during expiration
    • “can’t get air”
  10. Elastic Recoil
    • how easily the lungs bounce back after being stretched by inhalation
    • the HIGHER the elastic recoil, the stiffer the lungs
    • it's inversely related to lung compliance (LC): ↑EC means ↓LC
  11. Lung Compliance
    • a low compliance indicates a stiff lung & means extra work is required to bring in a normal volume of air
    • in contraction atelectasis, compliance decreases as the lungs become fibrotic, lose their distensibility, & become stiffer
  12. Which form of atelectasis is NOT reversible?
    • CONTRACTION atelectasis - can't remove the fibrotic change
    • the other 2 ARE reversible b/c you can remove the obstructing object (resorption) or fluid/air exerting pressure on the lung (compression)
  13. Acute Lung Injury (ALI)
    • a range of bilateral pulmonary lesions (endothelial & epithelial) that can be triggered by numerous conditions
    • aka caused by any stimulus of local or systemic inflammation (principally sepsis)
  14. Clinical Manifestations of Acute Lung Injury
    1. acute onset of dyspnea (shortness of breath, labored breathing)

    2. decreased arterial oxygen pressure (hypoxemia)

    3. development of bilateral pulmonary infiltrates on radiographs - aka fluid has leaked into alveolar space

    4. absence of clinical evidence of primary left-side heart failure (non-cardiogenic pulmonary edema w/ damage to alveolar capillary membrane)
  15. Hypoxemia
    an abnormally low level of oxygen (oxygen deficiency) in arterial blood
  16. What can Acute Lung Injury progress to?
    the more severe acute respiratory distress syndrome (ARDS)
  17. Acute Respiratory Distress Syndrome (ARDS)
    • a clinical syndrome of progressive respiratory insufficiency caused by diffused alveolar damage in the setting of sepsis, severe trauma (eg. inhaling hot air during a fire), & diffuse pulmonary infection
    • caused by diffuse alveolar damage (DAD*) involving the pulmonary capillaries & epithelium
    • involves an initial exudative phase followed by an organizing phase
    • used to be called “Shock” or "Wet" Lung
  18. Acute (Exudative) Phase
    • most characteristic finding: HYALINE membranes lining distended alveolar ducts (appear by day 2 & are most conspicuous after 4-5 days)
    • lungs are dark red, firm, airless, & heavy
    • capillaries are congested
    • alveolar epithelial cell necrosis (epith = type I pneumocytes)
    • interstitial & intra-alveolar edema & hemorrhage
    • collections of NEUTROPHILS in capillaries (esp. w/ sepsis)
  19. What are the hyaline membranes lining alveolar ducts that appear during the acute phase of ARDS made up of?
    • precipitated plasma proteins (fibrin etc.) + cytoplasmic & nuclear debris from sloughed epithelial cells
  20. Organizing Phase
    • begins ~1 week after initial injury
    • there is proliferation of fibroblasts within alveolar walls & of type II pneumocytes (like the lung stem cells) attempting to regenerate the alveolar lining
    • alveolar MACROPHAGES digest remnants of hyaline membranes + other cellular debris
    • resolution is unusual aka the lung will not return back to its pre-injured state
    • organization of the fibrin exudates occurs → intra-alveolar fibrosis
    • marked thickening of the alveolar septa is caused by proliferation of interstitial cells & deposition of collagen
  21. Common v. Rare Causes of Acute Respiratory Distress Syndrome
    • common: shock, pneumonia w/ sepsis, endotoxins, ischemia, aspiration of gastric contents
    • rare: inhalation of toxic gases or extremely hot air, radiation; near drowning, metabolic disorders (uremia, acidosis, acute pancreatitis, drugs etc.)
  22. How soon after an initiating insult will the majority of patients develop the clinical signs of ARDS?
    • 85% of patients will within 72 HOURS
    • mortality rate is ~40%
  23. Clinical Manifestations of Acute Respiratory Distress Syndrome
    • respiratory failure: rapid onset & life-threatening
    • cyanosis
    • acute onset of tachypnea & dyspnea
    • diffuse, bilateral, interstitial, & alveolar infiltrates are seen in radiographs
    • severe arterial hypoxemia that doesn't respond (is refractory) to oxygen treatment - mechanical ventilation must be used to force air in & out of the lungs
    • may progress to multi-system organ failure
    • people who are old, have underlying bacteremia (sepsis), or develop multi-system (esp. cardiac, renal, or hepatic) failure have a poor prognosis
    • alveolar hypoventilation, progressive hypoxemia, & increasing PCO2 lead to fatality
  24. Acute Respiratory Distress Syndrome Pathogenesis
    • diffuse alveolar damage: alveolar wall integrity is compromised by endothelial, epithelial, or injury to both
    • this injury is caused by an imbalance of pro-inflammatory & anti-inflammatory mediators
    • *nuclear factor κΒ shifts the balance in favor of a pro-inflammatory state
    • within 30 minutes after an initial assault, release of IL-8, IL-1, TNF, & other factors → endothelial activation, pulmonary microvascular sequestration, & activation of NEUTROPHILS
  25. What leukocytes are thought to have an important role in the pathogenesis of ARDS?
    • activated neutrophils release factors that cause damage to the alveolar wall & maintain the inflammatory cascade
    • endo & epithelium injuries → vascular leakage & loss of surfactant → render the alveolar unit unable to expand
  26. What does the degree of tissue injury & clinical severity of ARDS depend on?
    • the balance between the pro- & anti-inflammatory factors in the lungs
    • examples of anti-inflammatory factors: endogenous anti-proteases, antioxidants, anti-inflammatory cytokines
  27. What can be seen during the healing stage of ARDS?
    • absorption of hyaline membrane
    • thickened alveolar septa containing inflammatory cells, fibroblasts, & collagen
    • numerous atypical type II pneumocytes (arrows) are seen, & are associated w/ regeneration & repair
  28. What are some possible chronic sequelae (consequences) of ARDS?
    • scared lungs (diffused interstitial fibrosis), respiratory dysfunction, & in some cases pulmonary hypertension (arises from the scarring)
    • in an uncomplicated outcome normal respiratory function returns within 6-12 months
  29. Obstructive Pulmonary Diseases (OPD)
    • diseases of the airways characterized by limited AIRFLOW, which usually results from an increase in resistance caused by partial or complete obstruction at any level (eg. emphysema, chronic bronchitis, bronchiectasis, asthma etc.)
    • breathing difficulty may result from an airway narrowing or from a loss of elastic recoil
    • emphysema is based on morphology while chronic bronchitis is based on clinical features/symptoms
  30. Pure Chronic Bronchitis
    • affects both the large & small airways
    • disease in the large-airways is characterized by inflammation & MUCUS HYPERSECRETION (productive cough)
    • disease in the small-airways (bronchiolitis) is characterized by peribronchiolar fibrosis & AIRFLOW OBSTRUCTION due to inflammation
  31. Pure Emphysema
    • affects the acini (respiratory bronchiole, alveolar ducts, & alveoli) & is what causes the loss of elastic recoil
    • aka is alveolar wall destruction & overinflation
  32. Acinus
    • contains the structures distal to the terminal bronchiole (where there are no alveoli & no gas exchange) & includes several alveoli ducts & clusters of alveoli
    • (a lobule contains 3-5 acini)
  33. What 2 conditions usually coexist?
    • emphysema & chronic bronchitis - collectively referred to as COPD (chronic obstructive pulmonary disease)
    • characterized by irreversible airflow obstruction (the OPPOSITE of asthma)
    • affects both the large & small airways of >10% of the US adult population
    • is the 4th leading cause of death
    • asthma may be present in patients w/ COPD & is characterized by reversible airflow obstruction (opposite of COPD)
  34. Emphysema
    • COPD w/ irreversible airflow obstruction
    • is characterized by abnormal & permanent enlargement of the acini (airspaces distal to the terminal bronchioles)
    • is accompanied by destruction of their walls without obvious fibrosis
    • major cause: CIGARETTE SMOKING (is rare in non-smokers)
    • 2 types: centriacinar & panacinar (*the SEVERITY is more important than the type though)
  35. Emphysema Morphology
    • thinning/destruction of alveolar walls
    • adjacent alveoli become confluent → large airspaces
    • loss of elastic tissue in the surrounding alveolar septa → reduced radial traction on the small airways
    • (they tend to collapse during expiration which is an important cause of chronic airflow obstruction in severe emphysema)
    • a ↓ number of alveolar capillaries
  36. Centriacinar Emphysema
    • when the central or proximal portion of the acini, formed by the respiratory bronchioles, are affected while distal alveoli are spared
    • both normal & emphysematous airspaces exit within the same acinus & lobule
    • lesions are more common & severe in the UPPER lobes, particularly in the apical segments
    • can see destruction of alveolar walls WITHOUT fibrosis → enlarged air spaces
    • most commonly seen as a consequence of smoking in people who DON'T have a congenital deficiency of α-1-antitrypsin
    • is 20x more common than panacinar emphysema
  37. Panacinar Emphysema
    • acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind-ended alveoli (MORE destruction/loss of functional tissue than centriacinar)
    • enzymes destroy alveolar walls (eg. proteases, elastase)
    • occurs more commonly in the LOWER lung zones
    • the type of emphysema seen in people WITH an inborn α-1-antitrypsin deficiency
    • lungs can become quite voluminous (larger does NOT mean working better - will have a lower capacity for gas exchange b/c the surface area to volume ratio ↓)
  38. How many patients w/ congenital α-1-antitrypsin deficiency develop symptomatic panacinar emphysema?
    more than 80% of
  39. α-1-antitrypsin deficiency
    this leads to excessive amounts of trypsin, which is able during inflammatory processes to excessively digest elastin in the alveolar walls → dysfunction
  40. Emphysema Pathogenesis
    • can be thought of as resulting from insufficient tissue repair upon exposure to toxic substances (smoke/pollutants)
    • exposure induces ongoing inflammation w/ accumulation of NEUTROPHILS, MACROPHAGES, & LYMPHOCYTES in the lung
    • anti-inflammatory factors (endogenous anti-proteases like α-1-antitrypsin, antioxidants, anti-inflammatory cytokines) keep the inflammatory process in check
    • a loss of homeostasis → destruction of alveolar walls w/o adequate mesenchymal repair
  41. What causes epithelial injury & proteolysis of the ECM in Emphysema?
    • elastases
    • cytokines (eg. IL-8)
    • matrix metalloproteinases
    • release of oxidants
  42. Symptoms of Emphysema
    • symptoms appear after 1/3 of the functioning pulmonary parenchyma is damaged
    • 1st = dyspnea & progresses steadily
    • cough & wheezing (that can be confused with asthma)
    • cough & expectoration amount are extremely variable
    • weight loss is common & can be severe
    • classical presentation: barrel-chest, dyspneic, long exhales (prolonged expiration), sitting forward hunched-over, & breathing through pursed lips
  43. What is the key to diagnosing emphysema?
    • best measures expiratory airflow limitations & is the key to diagnosis
    • pink puffers: over ventilate & remain well oxygenated
  44. Having what conditions in conjunction with emphysema are associated with poor a prognosis?
    • cor pulmonale
    • congestive heart failure related to secondary pulmonary hypertension
  45. What causes death in the setting of emphysema?
    • respiratory acidosis
    • right-sided heart failure
    • massive collapse of the lungs secondary to pneumothorax
    • treatments = bronchodilators, steroids, bullectomy, lung volume reduction surgery, lung transplant
  46. Chronic Bronchitis
    • a persistent, productive cough that lasts for at least 3 months & occurs in 2 or more consecutive years in the absence of another identifiable cause
    • is common among cigarette smokers (90% of cases), urban dwellers, & people who work in "challenging environments"
    • defined by clinical symptoms (in contrast to emphysema, which is defined by the morphology of tissues affected by the disease)
  47. 3 Types of Chronic Bronchitis
    • Simple (most patients): productive cough raises mucoid sputum but airflow is not obstructed
    • Chronic Asthmatic (what patients w/ hyper-responsive airways have): intermittent bronchospasm + wheezing
    • Chronic Obstructive (seen in heavy smokers): chronic outflow obstruction, + evidence of emphysema
  48. What characterizes Chronic Bronchitis?
    • ↑ in size of the bronchial mucus-secreting apparatus
    • 1. hypersecretion of mucus begins in the large airways
    • 2. hyperplasia & hypertrophy of mucous secreting goblet cells
    • 3. ↑ ratio of mucous to serous cells
  49. What is the morphological basis of air flow obstruction in chronic bronchitis?
    • 1. ‘small airway disease’: induced by goblet cell metaplasia w/ mucus plugging of the bronchial lumen, inflammation, & bronchiolar wall fibrosis
    • 2. emphysema (basically just alveoli/gas exchange breakdown due to cell damage)
  50. Chronic Bronchitis Morphology
    • *enlargement of the mucus-secreting glands in the trachea & larger bronchi
    • hyperemic + swollen mucosal lining in the larger airways covered by layer of mucinous/mucopurulent secretions
    • smaller bronchi & bronchioles may be filled w/ similar secretions
    • ↑ Reid index (ratio of the submucosal gland layer thickness to that of the bronchial wall)
    • MONONUCLEAR (sometimes neutrophils but NOT eosinophils except in asthmatic bronchitis) inflammatory cells infiltrate the bronchial mucosa
    • chronic bronchiolitis (small airway disease): goblet cell metaplasia, mucus plugging, inflammation, & fibrosis
  51. Bronchiolitis obliterans (BO)
    • a rare and life-threatening form of non-reversible obstructive lung disease in which the bronchioles (small airway branches) are compressed and narrowed by fibrosis (scar tissue) & inflammation
    • can be indicative of sever cases of Chronic Bronchitis (part of its morphology)
  52. What causes the airway obstruction in Chronic Bronchitis?
    the peribronchiolar fibrosis & luminal narrowing
  53. Clinical Symptoms of Chronic Bronchitis
    • productive cough that lasts for many years that's initially more severe in winter
    • cough may become constant, exertional dyspnea, cyanosis supervene, & cor pulmonale may ensue
    • “blue bloater”: from the combination of cyanosis & edema secondary to cor pulmonale
    • acute respiratory failure in patients w/ advanced chronic bronchitis that consists of progressive hypoxemia & hypercapnia
    • Emphysema
  54. COPD Predominant Conditions

    *also the signature way "pink puffers" lean forward to make it easier for them to breath is b/c in this position they can use 'accessory muscles of respiration'
  55. Asthma
    • characterized by REVERSIBLE bronchoconstriction caused by airway hyper-responsiveness to a variety of stimuli
    • is a chronic inflammatory disorder of the airway that causes recurrent episodes of wheezing, breathlessness, chest tightness, & cough particularly at night &/or early in the morning
    • (obstructive pulmonary disease w/ REVERSIBLE airflow obstruction)
  56. What are the 3 main features of asthma?
    • 1. intermittent & reversible airway obstructions
    • 2. chronic bronchial inflammation w/ EOSINOPHILS
    • 3. bronchial smooth muscle cell hypertrophy
    • & hyper-reactivity
    • is caused by repeated immediate hypersensitivity & late phase reactions in the lungs
    • #3 is why smooth muscle relaxants can be used to combat an asthma attack
  57. Atopic (Extrinsic) Asthma
    • caused by a TH2 & IgE-mediated immunologic reaction to environmental allergens
    • is responsible for 70% of asthma cases
    • reaction is characterized by acute (immediate) & late-phase reactions
    • important mediators: TH2 cytokines IL-4, IL-5, & IL-13
  58. Non-atopic (Intrinsic) Asthma
    may be triggered by non-immune stimuli including aspirin, cold, psychological stress, exercise, viral infections, or inhaled air pollutants (eg. occupational asthma)
  59. What are key inflammatory cells found in ALL subtypes of asthma?
    • major basic protein from eosinophils are responsible for airway damage
    • airway remodeling (basement membrane thickening + hypertrophy of bronchial smooth muscle) adds to the degree of obstructive disease
  60. Airway Remodeling
    • thickening of the basement membrane of the bronchial epithelium
    • edema & an inflammatory infiltrate (EOSINOPHILS & MAST CELLS) in the bronchial walls
    • ↑ in submucosal gland size
    • hypertrophy of the bronchial muscle walls
    • *important histological feature seen in asthma
  61. Morphology of Asthma
    • occlusion of bronchi & bronchioles by thick, tenacious MUCUS PLUGS
    • histologically the mucusplugs contain whorls of shed epithelium called Curschmann spirals
    • EOSINOPHILS + Charcot-Leyden crystals (made up of eosinophil proteins)
    • Airway remodeling
  62. Asthma Symptoms
    • chief difficulty is w/ exhaling
    • severe dyspnea w/ wheezing
    • patient labors to get air into lungs then can't get it out
    • progressive hyperinflation of the lungs w/ air trapped distal to the bronchi (which are constricted & filled w/ mucous + debris)
    • lasts from 1 → several hours; subsides either spontaneously or w/ therapy
    • hypercapnia (↑ blood CO2), acidosis, severe hypoxia
    • status asthmaticus
  63. Status Asthmaticus
    when a severe paroxysm (attack) occurs, does not respond to therapy, & persists for days → weeks
  64. Bronchiectasis
    • the permanent dilation of the bronchi & bronchioles secondary to obstruction or persistent infection, both of which results in destruction of the smooth muscles & elastic supporting tissues in the wall of the airways
    • symptoms are dominated by cough & expectoration of copious amount of purulent sputum
    • is a consequence of ANOTHER disease process that destroys airways
  65. Causes of Bronchiectasis
    • 1. Bronchial Obstruction: tumors, foreign bodies, mucus plugs
    • 2. Congenital or Hereditary Conditions: Cystic fibrosis, Immunodeficiency states (↑ susceptibility to infection), Primary ciliary dyskinesia (poorly functioning cilia → recurrent infections) or Kartagener (Immotile Cilia) Syndrome
    • 3. Necrotizing or Suppurative Pneumonia: particularly with virulent organisms such as Staphylococcus aureus or Klebsiella
  66. Bronchiectasis Morphology
    • usually involves the LOWER lobes of the lungs bilaterally, particularly air passages that are most VERTICAL
    • airways may be dilated to 4x their normal size
    • in an active case: an intense acute & chronic inflammatory exudate within the walls of the bronchi & bronchioles + desquamation of epithelium lining → extensive ULCERATION
    • in such an environment, a mixed flora can be cultivated (fosters bacterial, viral, fungal growth)
    • FIBROSIS of the bronchial & bronchiolar walls
    • PERIbronchiolar fibrosis in more chronic cases
    • lung abscess may form
    • during healing the lining epithelium may regenerate completely HOWEVER abnormal dilation & scarring persist
    • more distal bronchi & bronchioles are more severely affected
  67. Bronchiectasis Symptoms
    • severe, persistent cough
    • expectoration of mucopurulent sputum
    • hemoptysis (coughing up of blood or blood-stained sputum) can occur
    • EPISODIC symptoms, which are often precipitated by upper respiratory tract infections
    • clubbing of the fingers
    • severe/widespread cases: significant obstructive ventilatory defects, hypoxemia, hypercapnia (↑ arterial CO2), pulmonary hypertension, & rarely cor pulmonale