The Lung

1
The Lung
2
Congenital Anomalies

• Agenesis or hypoplasia of both lungs, one lung,
  or single lobes
• Tracheal and bronchial anomalies (atresia,
  stenosis, tracheoesophageal fistula)
• Vascular anomalies
• Congenital lobar overinflation (emphysema)
• Foregut cysts
• Congenital pulmonary airway malformation
• Pulmonary sequestrations

3
Atelectasis (Collapse)

• Incomplete expansion of the lungs or collapse of
  previously inflated lung
• Three types
• Resorption (obstruction)
• Compression (e.g. tension pneumothorax)
• Contraction

4
Pulmonary Edema

• Table 15-1 - Classification and Causes of
  pulmonary edema
• Hemodynamic pulmonary edema
• Heart failure cells, brown induration
• Edema caused by microvascular injury

5
Acute Lung Injury and Acute Respiratory Distress
syndrome (Diffuse Alveolar Damage)

• Acute lung injury (ALI) -abrupt onset of
  significant hypoxemia and diffuse pulmonary
  infiltrates in the absence of heart failure
• Acute respiratory distress syndrome(ARDS)
  severe ALI
• Table 15-2 conditions associated with ARDS
• Acute interstitial pneumonia ALI of unknown
  etiology

6
Acute Lung Injury

• Diffuse alveolar damage, hyaline membranes
• Integrity of the alveolar capillary barrier is
  compromised by endothelial, epithelial injury, or
  more commonly, both
• Lung injury is caused by an imbalance of
  pro-inflammatory and anti-inflammatory mediators
• Clinical dyspnea and tachypnea, cyanosis and
  hypoxemia, respiratory failure, diffuse bilateral
  infiltrates, ventilation-perfusion mismatch

7
Obstructive vs Restrictive Diseases

• Obstructive
• Airway diseases
• Increase in resistance to airflow due to partial
  or complete obstruction
• Decreased FEV 1
• Emphysema
• Chronic bronchitis
• Asthma
• Bronchiestasis
• Bronchiolitis

• Restrictive
• Reduced expansion of the lung parenchyma and
  decreased total lung capacity
• Chest wall disorders
• Neuromuscular ( e.g. polio)
• Kyphoscoliosis
• Pleural Disease
• Severe obesity
• Chronic interstitial and infiltrative disease
• Pulmonary fibrosis
• Pneumoconioses
• Granulomatous diseases
• Pulmonary Eosinophila
• Pulmonary alveolar Proteinosis

8
Obstructive Pulmonary Disease

• Emphysema
• Chronic Bronchitis
• Asthma
• Bronchiectasis

9
Emphysema

• Irreversible enlargement of the airspaces distal
  to the terminal bronchiole, accompanied by
  destruction of their walls without obvious
  fibrosis
• Types
• Centriacinar
• Panacinar - alpha 1-antitrypsin deficiency
• Distal acinar spontaneous pneumothorax
• Airspace enlargement with fibrosis (Irregular)

10
Emphysema

• Pathogenesis
• Destructive effect of high protease activity in
  subjects with low antiprotease activity
• Oxidant-antioxidant imbalance
• Smoking

11
Emphysema

• Clinical dyspnea, cough, wheezing, weight loss,
  expiratory airflow limitation (spirometry), pink
  puffers, death due to respiratory acidosis,
  right-sided heart failure, massive collapse of
  lungs secondary to pneumothorax
• Other forms
• Compensatory hyperinflation
• Obstructive overinflation
• Bullous emphysema
• Interstitial emphysema

12
Chronic Bronchitis

• Persistent cough with sputum production for at
  least 3 months in at least 2 consecutive years,
  in the absence of any other identifiable cause
• Table 15-4 Emphysema and chronic bronchitis
• Pathogenesis
• Long-standing irritation by inhaled substances
• Hypersecretion of mucus, hypertrophy of glands,
  hyperplasia of goblet cells of small airways
  (Reid index)
• Infection secondary role
• Blue-bloaters

13
Asthma

• Chronic inflammatory disorder of the airways that
  causes recurrent episodes of wheezing,
  breathlessness, chest tightness, and cough
  particularly at night and/or early morning
• Widespread but variable bronchoconstriction and
  airflow limitation, that is at least partially
  reversible
• Increased airway responsiveness to a variety of
  stimuli, episodic bronchoconstrition,
  inflammation of the brochial walls, increased
  mucus secretion

14
Asthma

• Types
• Atopic type I IGE-mediated hypersensitvity
• Non-atopic viral-induced
• Drug-induced - aspirin
• Occupational fumes, dust, chemicals

15
Asthma

• Curschmann spirals
• Charcot-Leyden crystals
• Airway remodeling
• Clinical dyspnea, tightness, wheezing, cough,
  status asthmaticus

16
Bronchiectasis

• Permanent dilation of bronchi and bronchioles
  caused by the destruction of the muscle and
  elastic tissue, resulting from or associated with
  chronic necrotizing infections
• Dilated airways up to four times normal size
• Mixed flora from bronchi
• Clinical severe, persistent cough,
  foul-smelling, sometimes bloody sputum, dyspnea
  and orthopnea

17
Chronic Diffuse Interstitial (Restrictive)
Diseases

• Fibrosing diseases
• Idiopathic Pulmonary fibrosis
• Nonspecific interstitial pneumonia
• Crytogenic Organizing pneumonia
• Pulmonary involvement in the Connective tissue
  diseases
• Pneumoconioses
• Complications of therapies
• Granulomatous Diseases
• Sarcoidosis
• Hypersensitivity pneumonitis
• Pulmonary eosinophilia
• Smoking-related Interstitial diseases
• Desquamative interstitial pneumonia
• Respiratory Bronchioloiis associated
  interstitial lung disease
• Pulmonary Alveolar Proteinosis

18
Chronic Diffuse Interstitial Diseases

• Inflammation and fibrosis of the pulmonary
  connective tissue, principally the most
  peripheral and delicate interstitium in the
  alveolar walls
• Table 15-5 Major categories of chronic
  interstitial lung disease

19
Fibrosing Diseases

• Idiopathic pulmonary fibrosis
• Also called cryptogenic fibrosing alveolitis
• Caused by repeated cycles of epithelial
  activation/injury by some unidentified agent
• Patchy interstitial fibrosis, honeycomb
• Clinical DOE and cough, hypoxemia, cyanosis,
  clubbing

20
Fibrosing Diseases

• Cryptogenic organizing pneumonia
• Bronchiolitis obliterans organizing pneumonia
• Polypoid plugs of organizing connective tissue
  within alveolar ducts, alveoli, bronchioles
• Nonspecific Interstitial pneumonia
• Cellular pattern better prognosis
• Fibrosing pattern similar to UIP
• No honeycombing

21
Pneumoconioses

• Coal Workers pneumoconioses
• Asymptomatic anthracosis
• Simple with little to no pulmonary dysfunction
• Complicated
• Progressive massive fibrosis
• Coal macules, coal nodules, centrilobular
  emphysema

22
Silicosis

• Silica (silicon dioxide) quartz most fibrogenic
• The most prevalent chronic occupational disease
  in the world
• Eggshell calcification, hard, collagenous scars
• Inreased suseptibility to TB

23
Asbestos-related DIseases

• Localized fibrous plaques or rarely, diffuse
  pleural fibrosis
• Pleural effusions
• Parenchymal interstitial fibrosis (asbetosis)
• Lung carcinoma
• Mesotheliomas
• Laryngeal and perhaps other extrapulmonary
  neoplasms ( e.g. colon carcinomas

24
Complications of Therapies

• Drug-induced Table 15-7
• Radiation-induced
• Radiation pneumonitis fever, dyspnea, pleural
  effusion,infiltrates

25
Granulomatous Diseases

• Hypersensitivity pneumonitis
• Prolonged exposure to inhaled organic agents,
  farmers lung, pigeon breeders lung, type IV
  hypersensitivity, granulomas
• Sarcoidosis
• Noncaseating granulomas, bilateral hilar
  adenopathy, eye and skin involvement, anergy,
  polyclonal hypergammaglobulinemia

26
Pulmonary Eosinophilia

• Acute eosinophilic pneumonia with respiratory
  failure
• Simple pulmonary eosinophilia or Loffler syndrome
• Tropical eosinophilia, caused by infection with
  microfilariae
• Secondary eosinophilia
• Idiopathic chronic eosinophilic pneumonia

27
Smoking-related Interstitial Diseases

• Smokers macrophages
• Desquamative interstitial pneumonia
• Respiratory bronchiolitis-associated interstitial
  lung disease

28
Pulmonary Alveolar Proteinosis

• Accumulation of acellular surfactant in the
  intra-alveolar and bronchiolar spaces,
  homogeneous granular precipitate within the
  alveoli
• Three classes
• Acquired
• Congenital
• Secondary

29
Pneumoconioses

• Table 15-6 - Lung diseases caused by air
  pollutants
• Development og pneumoconiosis depends on
• Amount of dust retained in the lung and airways
• Size, shape, and buoyancy of the particles most
  dangerous 1-5um in diameter because they may
  reach the terminal small airways and air sacs and
  settle in their linings
• Possible additional effects of other irritants

30
Disorders of Vascular Origin

• Pulmonary embolism, hemorrhage and infarction
• Pulmonary hypertension
• Diffuse pulmonary hemorrhage syndromes
• Goodpasture syndrome
• Idiopathic pulmonary hemosiderosis
• Wegener granulomatosis

31
Disorders of Vascular Origin

• Blood clots that occlude the large pulmonary
  arteries are almost always embolic in origin
  95 from deep veins in the legs
• Large pulmonary embolus is one of the few causes
  of instantaneous death, electromechanical
  dissociation
• Wedge-shaped infarction
• Unresolved, multiple small emboli over the course
  of time may lead to pulmonary hypertension
• Patients with a pulmonary embolus have a 39
  chance of developing a second embolus

32
Pulmonary Hypertension

• Occurs when pulmonary pressure reaches ¼ systemic
  ( usually about 1/8)
• Chronic obstructive or interstitial lung diseases
• Antecedent congenital or acquired heart disease
• Recurrent thromboemboli
• Connective tissue disease
• Obstructive sleep apnea
• Idiopathic
• Familial form (BMPR2 signaling pathway)
• Medial hypertrophy of muscular and elastic
  arteries, atheromas formation, plexiform lesions

33
Pulmonary Infections

• Loss or suppression of the cough reflex
• Injury to mucociliary apparatus
• Accumulation of secretions
• Interference with phagocytic or bactericidal
  action of alveolar macrophages
• Pulmonary congestion and edema
• Immunodeficiencies
• One type of pneumonia sometimes predisposes to
  another, especially in debilitated patients
• Many patients with chronic diseases acquire
  terminal pneumonias while hospitalized

34
Pulmonary Infections

• Community-acquired acute pneumonias
• Community acquired atypical (viral and
  mycoplasmal) pneumonias
• Hospital-acquired pneumonia
• Aspiration pneumonia
• Lung Abscess
• Chronic pneumonia
• Pneumonia in the immunocompromised host
  infiltrate with/without fever
• Pulmonary disease in HIV infections CD4 counts

35
Community Acquired Pnemonias

• Acute pnemonia
• Lobar
• Consolidation
• Bacterial
• Streptococcus
• HIB
• Moraxella catarrhalis
• S. aureus
• Legionella
• Klebsiella
• Pseudomonas

• Atypical Pneumonia
• Interstitial
• Patchy
• Walking pneumonia
• Mycoplasma
• Chlamydia
• Coxiella ( Q fever)
• Viruses

36
Bacterial pneumnia

• Lobar pneumonia stages of inflammation -
  fibrinosuppurative
• Congestion
• Red hepatization
• Gray hepatization
• Resolution
• Complications
• Abscess formation
• Empyema
• Bacteremic dissemination

37
Lung Abscess

• Local suppurative process within the lung,
  characterized by necrosis of lung tissue
  central area of cavitaiton
• Aspiration of infective materials
• Antecedent primary lung infection
• Septic embolism
• Neoplasia
• Miscellaneous

38
Chronic Pneumonia

• Often a localized lesion in a immunocompromised
  patient
• Typically granulomatous
• Fungal pneumonias
• Resemble TB
• Thermally dimorphic - hyphae, spores in
  environment but yeasts at body temperatures
• Geographic
• Histoplasmosis Ohio and Mississippi river
  valleys and Caribbean
• Blastomycosis Central and southeastern US
• Coccidoidomycosis Southwest and far west US and
  Mexico

39
Lung Transplantation

• Indications
• End-stage emphysema
• Idiopathic pulmonary fibrosis
• Cystic fibrosis
• Idiopathic/familial pulmonary arterial
  hypertension
• Rejection
• Acute often similar to infection, biopsy needed
• Chronic bronchiolitis obliterans
  disappointing survival rate

40
Tumors

• Carcinomas
• Neuroendorine proliferations and tumors -
  carcinoid
• Miscellaneous tumors Table 15-13 Mediastinal
  tumors and other masses
• Metastatic tumors lung most common site of
  metastatic neoplasms

41
Carcinomas

• Tobacco smoking
• Industrial hazards
• Air pollution
• Molecular genetics
• c-MYC, KRAS, EGFR, c-MET, c-KIT

42
Carcinomas

• Precursor lesions
• Squamous dysplasia and carcinoma in situ
• Atypical adenomatous hyperplasia
• Diffuse idiopathic pulmonary neuroendocrine cell
  hyperplasia
• Classifications Table 15-10
• Adenocarcinoma women, non-smokers, EGFR
• Squamous cell carcinoma - smokers
• Small cell carcinoma - smokers
• Large cell carcinoma

43
Carcinomas

• Clinical cough, weight loss, chest pain,
  dyspnea, most around hilus of the lung,
  bronchioloalveolar not invasive
• Local effects Table 15-12
• Staging Table 15-11
• Paraneoplastic
• SIADH
• Cushing
• Hypercalcemia
• Gynecomastia
• Carcinoid syndrome
• Lambert-Eaton myasthenic
• Peripheral neuropathy
• Acanthosis nigricans
• Leukemoid reactions
• Hypertrophic pulmonary osteoarthropathy (
  clubbing)

44
Pleura

• Pleural effusions
• Inflammatory pleural effusions
• Noninflammatory pleural effusions
• Hydrothorax
• Hemothorax
• Chylothorax
• Pneumothorax
• Emphysema, asthma, TB, spontaneous
• Pleural tumors
• Solitary fibrous tumor
• Malignant mesothelioma

45
(No Transcript)