Respiratory Diseases Part 1

Front 1

Emphysema - Understand mechanism of airflow obstruction in emphysema

Back 1

- Profound physiologic alterations resulting from loss of alveolo-capillary membrane
- manifested as dyspnea, increased work of breathing, hypoxemia
- Loss of airway caliber and/or radial traction
- Obstructive pattern --> low FEV-1, increased TLC, mild hypoxemia, hypercapnia late stages

Front 2

Emphysema - Appreciate tobacco role in pathophysiology of emphysema

Back 2

Pathogenesis:
- alpha 1 antitrypsin deficiency or smoking results in a decrease in a1 antitrypsin (protease inhibitor) which normally prevents elastic tissue damage (by protecting against neutrophil elastase), without it, it leads to destruction and emphysema. Smoking also increases Elastase which is a protease that breaks down proteins leading to further damage and emphysema.
- smoking increases neutrophils --> more elastase and oxidants (inhibit alpha-1-antitrypsin); more macrophages --> enhanced elastolytic activity

Front 3

Emphysema - Knowledgeable on histopathology of emphysema

Back 3

Normal:
- bronchiole - simple columnar epithelium --> goes to alveoli Type I and II pneumocytes (capillary endothelial cell nuclei, scattered lymphocytes, mesenchymal cells, macrophages)
Hallmark of disease
- destruction of alveolar lung tissue
- ENLARGED SPACES w/ "FLOATING" PARENCHYMAL FRAGMENTS
- Focal subpleural scars

Gross:
- moth eaten appearance, destruction of lung parenchyma

Front 4

Emphysema - Types

Back 4

- Centrilobular: MAJOR - Focused on center of secondary lobule - smoking related, chronic bronchitis, black pigment
- Pan Lobular: Major - Entirety of secondary lobule involved, Alpha 1-anti-trypsin, less common
- Bullous: Minor - clinically important --> rupture of bullous --> Pneumothorax
- Paraseptal: Minor - Associated w/ fibrosis --> spontaneous pneumothorax in young adults

Front 5

Emphysema - Clinical

Back 5

- Pink Puffer; Older (60-70), tall, thin, cor pulmonale and hypercapnia in late stages; DLCO reduced; airway obstruction severe
- largely preventable but irreversible

Front 6

Restrictive Lung Disease - PFTs and characteristics

Back 6

- TLC < 80% (and VC); FEV/FVC ratio normal; DLCO depends on acute vs chronic

Front 7

Restrictive Lung Disease - Physiology and Pathophysiology (GENERAL)

Back 7

Physiology:
- Balance between forces of inspiratory muscles and recoil of lung and chest wall at max inspiration

Pathophysiology:
- Anything that weakens inspiratory muscles or put muscles at mechinal disadvantage; increases recoil forces of lung or chest wall
- abnormal lung parenchyma --> impairs O2 transfer --> muscles unable to maintain adequate alveolar ventilation; no more ventilatory reserve --> respiratory failure

Front 8

Restrictive Lung Disease - Extra-Parenchymal

Back 8

- Impaired muscle function
- Chest wall stiff --> increase recoil; Obesity; Kyphoscoliosis; Fluid filled abdominal cavity, pleural space --> impedes diaphragm
- Neuromuscular disorders; Pneumothorax; Pleural Effusion; Obstruction of major bronchus
Clinical Picture:
- Acute or chronic respiratory failure; dyspnea; decreased exercise tolerance; DLCO normal (usually); repeated infections; PAH

Front 9

Restrictive Lung Disease - Parenchymal

Back 9

- Any process that deposits materal in interstitium or alveoli --> decreases compliance of lung, increasing lung elastic recoil
- Edema or inflammatory cell infiltration of interstitium/alveolar space --> Fibrosis?
Acute:
- Rapid deteriorations due to swift transfer of fluid or cells to interstitium --> DAD
- changes in DLCO --> major trauma, fever, meds, exposure to toxic gases, cardiac problems, vascular disease
- presence/absence of fever and evidence of LVF --> helpful to narrow Dx
Chronic:
- Fibrosis (many causes); rely on history/etiology
- LVF, PAH, crepitations over lung fields, clubbing, joint findings, IV drug abuse
- increased interstitial markings: diffuse, finely nodular, reticular or reticulonodular
- DLCO decreases
Treatment:
- Difficult once fibrosis starts; remove from offending agent (if present); corticosteroids

Front 10

Interstitial Lung Disease - Specifics: Drug Induced

Back 10

Clinical:
- Exposure history, eosinophilia (peripheral)
Histology:
- NSIP, fibrosis
Required for Dx:
- Hx; response to cessation of drug and Tx w/ steroids

Front 11

Interstitial Lung Disease - Specifics: IPF

Back 11

Clinical:
- 5th-6th decade; insidious onset DOE; relentlessly progressive; predominantly lower lobes
Histology:
- UIP
Dx:
- Process of elimination, histology

Front 12

Interstitial Lung Disease - Specifics: Sarcoidosis

Back 12

Clinical:
- Bilateral symmetric hilar adenopathy; 20-30 year old big swollen lymph nodes; 75% resolves on own, 20% steroids, tiny percentage unresponsive to treatment
Histology:
- Multiple, tightly formed, uniform noncaseating granulomas
Dx:
- Lofgren's Syndrome; Compatible Hx and histology w/o explanation and no infection

Front 13

Interstitial Lung Disease - Specifics: HSP

Back 13

Clinical:
- Exposure Hx to known antigen peripheral eosinophila unusual
Histology:
- inflammation; loose granulomas
Dx:
Histology

Front 14

Interstitial Lung Disease - Interstitium

Back 14

- Lung compartment that contains interalveolar wall, cells within, basement membrane, collagen, capillaries

Front 15

Interstitial Lung Disease - IPF/UIP General/Radiology

Back 15

- Chronic, parenchymal; Restrictive - FEV/FVC normal --> but both decrease; TLC and VC decreased; severe hypoxemia
- Unknown etiology --> autoimmune suspected
- Chronic inflammatory disease of alveolar wall that distorts and destroys lung architecture w/ progressive severe fibrosis
Radiology
- Reticulonodular infiltrates

Front 16

Interstitial Lung Disease - IPF/UIP Pathogenesis

Back 16

- Epithelial Activation/Injury --> TGF - B1 --> Fibroblasts and myofibroblasts --> deposition of collagen and extracellular matrix --> Pulmonary Fibrosis

Front 17

Interstitial Lung Disease - IPF/UIP Clinical Course

Back 17

- Insiduous onset AND progression; DOE, dry cough, crackles
- 40-70 yrs old
- acute exacerbations; mean survival 3-5 yrs from diagnosis
GROSS:
- Lungs small, contracted, cirrhotic; externally cobblestoned; consistency is firm, rubbery; honeycomb
Histological:
- Patchy interstitial fibrosis; worst subpleurally and at basis of lungs (center spared); honeycomb
- Spatial disuniformity; Fibroblastic Foci (centers of fibroblastic activity)

Front 18

Interstitial Lung Disease - IPF/UIP Diagnosis/Outcome/Treatment

Back 18

- Clinical presentation; CT; PFT's; TISSUE IS THE ISSUE; presence of collagen fibrosis
Outcome:
- Short life expectancy
Tx:
- Newer anti-fibrotic agents targeting TGF - B1; Transplantation

Front 19

Sarcoid - Definition

Back 19

- Systemic chronic inflammatory disorder of unknown etiology
- Non-caseating granulomas; any organ of body (lung, mediastinal and hilar lymphnodes most common) then eye and skin
- Multifactorial (immunological factors, environmental factors, genetic)

Front 20

Sarcoid - Pathogenesis

Back 20

Immunologic
- Exaggerated Th1 cell response --> CD4:CD8 --> 5-15; increased Th1 cytokines in alveoli and interstitium; polyclonal hyperglobulinemia
Environmental
- Microbial orgs (mycobacteria, Rickettsie, propionibacterium)
Genetic
- Familial and racial clusterings HLA (A1 and B8)

Front 21

Sarcoid - Clinical manifestations & 2 related syndromes (SKIN; EYE and PAROTID)

Back 21

- <40 yrs old; blacks>whites; females>males;
- asymptomatic-->incidental finding; majority have respiratory symptoms; ERYTHEMA NODOSUM and LUPUS PERNIO; visual disturbances, arthralgia, parotid enlargement, hepatomegaly, cardiac dysrhythmias
SKIN Lesions
Erythema Nodosum - acute sarcoidosis; raised, red, tender bumps or nodules on anterior legs; Lofgren's Syndrome (fever, bilateral hilar adenopathy, e. nodosum, polyarthralgia --> remit 1-2 months
Lupus Pernio - Chronic Sarcoidosis; indurated plaques w/ discoloration of nose, cheeks, lips and ears; spontaneous remission rare
EYE and PAROTID Lesions
Heerfoldt's Syndrome - fever, anterior uveitis, parotid enlargement, facial palsy

Front 22

Sarcoid - Radiographic stages

Back 22

Stage O: Normal Chest Radiograph
Stage 1: Bilateral Hilar Lymphadenopathy ONLY (40%)
Stage 2: Bilateral Hilar Lymphadenopathy and Parenchymal Lung Disease (37%)
Stage 3: Parenchymal Lung Disease Only
Stage 4: Advanced parenchymal lung disease (fibrosis, honeycomb, cysts, bullae, traction bronchiectasis)

Front 23

Sarcoid - Histopathologic and Lab Findings

Back 23

- Restrictive PFTs, decreased DLCO; Obstructive if endobronchial sarcoidosis is present
Clinical
- Elevated ACE; hypercalcemia, hypercalciuria, hypergammaglobulinemia, elevated CD4 T cells in BAL fluid
GROSS:
- Stage dependent; small nodules w/ white-yellowish cut surface in lung parenchyma distributed in lymphangitic pattern) --> late stage extensive fibrosis
Histologic:
- Asteroid bodies, Schaumann's bodies, Calcium oxylate crystals

Front 24

Sarcoid - DDx and common pitfalls

Back 24

Dx:
- Compatible clinical and radiographic manifestations; histologic non-necrotizing granulomas; exclusion of other diseases causing granulomatous disease
DDX:
- Infectious microogranisms causing granulomatous inflammation (M. Tb); inhaled organic dust particles (Berrylium); Inhaled organic dust particles (HSP)

Front 25

Sarcoid - Prognosis

Back 25

- Unpredictable; 65-70% minimal or no residual manifestations; 20% have permanent loss of some lung function or eye impairment; 10-15% die of pulmonary fibrosis, cor pulmonale, cardiac arrhythmias or CNS abnormalities
Tx: Steroid or Immunosuppresant

Front 26

Lung Cancer - Etiology

Back 26

- 85% or more cases due to cigarette smoking (asbestos, radon gas, ionizing radiation, uranium, chemical exposure)
- arise by stepwise accumulation of genetic abnormalities that transform benign bronchial epithelium to neoplastic tissue (normal -> hyperplasia -> dysplasia (mild, moderate, severe) -> cancer)
- Most metastatic lesions are multiple while primary tumors are solitary masses
- Centrally located = easier to access via bronchoscopy

Front 27

Lung Cancer - Classification

Back 27

Non-Small Cell carcinoma
- Squamos cell carcinoma, adenocarcinoma, large cell carcinoma
- Important distinction bewteen adeno and squamos --> adeno patients eligible for molecular-targeted therapies and certain chemotherapeutic agents
Small Cell Carcinoma
- Classic, Mixed (small and large), Combined (adeno ca., squamos cell ca.)

Front 28

Lung Cancer - Squamos Cell Carcinoma (General, types, histology)

Back 28

- 25-40% of primary lung cancers; 80% occur in males; centrally located; obstructive pneumonitis; cavitated tumors
- Papillary, clear cell, small cell, basaloid
Histology
- Whitish bronchial mass; "pavement-like" appearance; desmosomes holding cells together; central necrosis; dark nuclei = malignant cells; KERATIN formation

Front 29

Lung Cancer - Adenocarcinoma (General, Types, Histology)

Back 29

- Malignant epithelial tumor w/ glandular differentiation and/or mucin production; 25-40% primary lung cancers (less association w/ smoking); peripheral location; fibrosis and scarring; 50% of lung cancers in women; 77% involve pleura, stimulates mesothelioma
- Bronchioloalveolar (important morphology), acinar, papillary, solid, micropapillary
- Forms tubules and glands (papillary structures in some cases)
Histology
- Glandular involvement, mucin, acinar
Adenocarcinoa In Situ - bronchioloalveolar carcinoma --> growth along alveolar septae so lung architecture left intact --> diffuse infiltrates mimicking pneumonia (NO stromal, vascular, or pleural invasion)

Front 30

Lung Cancer - Large Cell Carcinoma

Back 30

- Undifferentiated non-small cell carcinoma w/o evidence of glandular or squamos differentiation (10-15% primary lung cancers)
GROSS:
- "Nice" distinct mass w/ clear borders
Histology:
- Prominent nucleoli and purple cytoplasm; clear cell variant, rhabdoid variant (cytoplasm one side, nucleus on other),

Front 31

Lung Cancer - Small Cell (Oat) Carcinoma

Back 31

- Malignant epithelial tumor composed of small cells (less than 3 lymphocytes) w/ scant cytoplasm, ill defined cell borders, finely granular nuclear chromatin, and absent or inconspicuous nucleoli.
- High nuclear:cytoplasm ratio; nuclear molding; NEUROSECRETORY GRANULES --> neuroendocrine differentiation (SIADH)
- IMPORTANT - Much greater metastatic potential, but responds better to chemotherapy.
- 20-25% primary lung cancers
- Centrally located --> around airways

Front 32

ARDS/DAD - Relation of the two…

Back 32

- ARDS typically presents with rapidly progressive respiratory failure and DAD is the histopathologic pattern most commonly encountered in ARDS
- ARDS occurs 24-48 hours after initiating event --> profound hypoxemia requiring mechanical ventilation

Front 33

ARDS - Initiating Events

Back 33

Major:
- Sepsis, Trauma, Shock or combination
- Sepsis and Shock accompanied by release of endotoxins
Minor:
- Fat emboli; acute pancreatitis; chemicals; others
- Hamman-Rich syndrome --> idiopathic start, aka acute interstitial pneumonia

Front 34

DAD - Radiologic Findings

Back 34

- Airspace consolidation; initially patchy, but rapidly progressing to diffuse; linear opacities may develop later (fibrosis)
- Bilateral lungs w/ ground glass opacities

Front 35

DAD - Pathophysiology

Back 35

- VASCULAR LEAK --> permeability edema (no increase in hydrostatic pressure, leak is due to structural damage
FYI: Other causes of pulmonary edema = Non Cardiogenic Edema and Cardiogenic Edema

Front 36

DAD - Clinical

Back 36

- Severe dyspnea, hypoxemia
- Rapidly progressive respiratory failure
- Mechanical ventilation

Front 37

DAD - Gross

Back 37

Exudative Phase - Heavy, dark, red, consolidated
Proliferative Phase - Firm, yellow-gray, airless
- Exudation of fluid throughout
- Lungs remain heavy and develop a grayish color throughout

Front 38

DAD - Microscopic

Back 38

- Edema fluid in air spaces
- HYALINE MEMBRANES
Exudative Phase:
- 5-7 days after initial injury (widening septa and hyaline membranes)
- HM are eosinophilic and have refractile quality --> HM peak (4-5 days) and become well established
- sparse inflammation
Proliferative Phase
- Prominent (atypical) type II cells; squamos metaplasia
- grayish-blue "myxoid" interstitial fibrosis
Fibrotic phase
- Fibrosis

Front 39

DAD - DDx, Prognosis, Outcome

Back 39

DDx:
- NSIP, UIP (acute exacerbation), COP (cryptogenic organizing pneumonia)
Prognosis:
- Mortality 40-60%
Outcome:
- Survivors --> normal PFT 6-12 months; some, however, retain RESTRICTIVE deficit

Front 40

Obstructive Lung Disease - Spirometry/Diseases/Mechanism of Respiratory Failure

Back 40

- Decreased FEV1/FVC; decreased TLC, decreased DLCO
- Asthma (intermittent/reversible), Chronic Bronchitis (irreversible), Emphysema (irreversible), Bronchiectasis
- V/Q mismatch and narrowed airway caliber --> increased work of breathing (increased airway resistance, minute ventilation, air trapping, and suboptimal muscle mechanics) --> Respiratory Failure
- Dynamic hyperinflation

Front 41

Obstructive Lung Disease - COPD Epidemiology

Back 41

- >10 mil; 3/4 chronic bronchitis; Smoking

Front 42

Obstructive Lung Disease - COPD Clinical Picture

Back 42

- 25-30 pack years
- cough, wheezing, shortness of breath, hyperinflation of lungs, long expiratory phase
- digital clubbing in severe/complicated cases, accessory muscle use, pursed lip breathing; PAH and cor pulmonale
Bronchitis:
- productive cough, 3 consecutive months, in each of 2 consecutive years, hemoptysis

Front 43

Obstructive Lung Disease - COPD Radiology

Back 43

- Decreased lung markings (swiss cheese) and hyperinflation
- Bullae in upper lobes

Front 44

Obstructive Lung Disease - COPD Natural History - Progression

Back 44

- FEV1 normally declines w/ age, smoking accelerates that decline.
- Smoking cessation returns decline rate to normal, but amount declined is not made up
- Amount of functional reserve determines course of illness

Front 45

Obstructive Lung Disease - COPD Complications

Back 45

- Pulmonary Hypertension (chonic hypoxic pulmonary vasoconstriction)
- Right ventricular overload/failure (cor pulmonale)
- Pneumothorax
- DVT/PE

Front 46

Obstructive Lung Disease - COPD Treatment

Back 46

- Smoking cessation!
- Bronchodilators (beta2agonists, anticholinergics, theophylline - not used)
- Corticosteroids (acute exacerbations and use may help slow rate of decline in FEV1)
- Antibiotics, Supplemental O2, Pulmonary Rehab

Front 47

Obstructive Lung Disease - Asthma

Back 47

- Chronic Inflammatory disorder w/ recurrent episodes of sx's, variable airflow limitation and increased airway responsiveness
- No cure, can be controlled
- Eosinophilic bronchiolitis; airway narrowing; bronchial hyperactivity; desquamation of epithelium

Front 48

Obstructive Lung Disease - Asthma Control and Morbidity/Mortality factors

Back 48

- Suppress and reverse INFLAMMATION
- Morbidity and Mortality due to underdiagnosis and inappropriate treatment

Front 49

Obstructive Lung Disease - Asthma Airway Obstruction

Back 49

- Smooth muscle hypertrophy/spasm
- Hypertrophy of mucous glands and goblet cells --> mucosal plugging
- Airway wall edema

Front 50

Obstructive Lung Disease - Asthma Pathophysiology / Ominous signs

Back 50

- Hypoxemia; respiratory alkalosis; "Normal" pH/PaCO2 ominous sign
Other ominous signs:
- Upright body posture, unable to lie flat; diaphoresis; accessory muscle use; pulsus paradoxus > 20 mmHG

Front 51

Obstructive Lung Disease - Asthma Therapy

Back 51

- Supportive --> O2; Trigger avoidance
Specific:
- Anti-inflammatories: corticosteroids, leukotriene modifiers; anti-IgE
- Bronchodilators: B2-Agonists, anticholinergics
- Mechanical Ventilation