Pathology Flashcards
(218 cards)
1
Q
What air obstructive airway diseases?
A
- Asthma
- COPD (chronic bronchitis, emphysema)
- Bronchiectasis (obstructive or mixed)
- Cystic fibrosis (obstructive or mixed)
2
Q
What is the definition of asthma?
A
- chronic inflammatory disorder of the airways resulting in episodes of reversible bronchospasm causing airflow obstruction
- associated with reversible airflow limitation and airway hyper-responsiveness to endogenous or exogenous stimuli
3
Q
At what oxygen saturation can you detect central cyanosis?
A
Central cyanosis is not detectable until SaO2 is <85%. It is more easily detected in polycythemia and less readily detectable in anemia
4
Q
What is the pathophysiology of how someone becomes acidotic in asthma?
A
• airway obstruction → V/Q mismatch → hypoxemia → increased ventilation → decreased PaCO2 → increased pH and muscle fatigue → decreased ventilation, increased PaCO2/decreased pH
5
Q
Asthma triggers
A
- URTIs
- Allergens (pet dander, house dust, moulds, cockroach)
- Irritants (cigarette smoke, air pollution)
- Drugs (NSAIDs, β-blockers)
- Preservatives (sulphites, MSG)
- Other (emotion/anxiety, cold air, exercise, GERD)
6
Q
Asthma signs and symptoms
A
- dyspnea, wheezing, chest tightness, cough, sputum
- symptoms usually occur or worsen at night
- symptoms can be paroxysmal or persistent
- signs of respiratory distress
- pulsus paradoxus
7
Q
Criteria for determining if asthma is well controlled
A
Daytime symptoms <4 d/wk No asthma-related absence from work/school Night-time symptoms <1 night/wk β2-agonist use <4 times/wk Physical activity unimpared by symptoms FEV1 or PEF >90% of personal best Exacerbations mild, infrequent PEF diurnal variation <10-15%
8
Q
PFT criteria for asthma diagnosis
A
FEV1/FVC <0.75-0.8 in adults and <0.8-0.9 in children
AND
Increase FEV1 ≥12% and, 200 mL in adults after bronchodilator or controller therapy
9
Q
What are challenge tests that can be used to diagnose asthma?
A
- Methacholine - PCO2 <4 mg/ml (4-16 is borderline, >16 is negative)
- Post exercise decrease in FEV1 10-15%+
10
Q
Asthma treatment
A
- environment: avoid triggers
- patient education: features of the disease, goals of treatment, self-monitoring
• pharmacological
■ symptomatic relief in acute episodes: short-acting β2-agonist, anticholinergic bronchodilators, inhaled corticosteroids, addition of a long acting β2-agonist
■ long-term maintenance: inhaled/oral corticosteroids, anti-allergic agents, long-acting β2-agonists (do not use LABA alone), long-acting anticholinergics, methylxanthine, LTRA, anti-IgE antibodies (e.g. omalizumab), anti-IL5 drugs (e.g. mepolizumab)
11
Q
Emergency management of asthma
A
- inhaled β2-agonist first line (MDI route and spacer device recommended)
- systemic steroids (PO or IV if severe)
- if severe add anticholinergic therapy ± magnesium sulfate
- rapid sequence intubation in life-threatening cases (plus 100% O2, monitors, IV access)
- SC/IV adrenaline if caused by anaphylaxis, IV salbutamol if unresponsive
- corticosteroid therapy at discharge
12
Q
What asthma medication is good to try if the patient is having night time symptoms
A
LABA
13
Q
Use of LTRA in acute asthma
A
Currently, there is no evidence to support routine use of LTRAs in acute asthma.
14
Q
Asthma pyramid guidelines
A
Confirm diagnosis
Environmental control, education, written action plan
SABA or ICS/LABA on demand
ICS
2nd line: LTRA
12+ years: add LABA
6-11 years: increase ICS
12+ years: add LTRA (apparently LTRA doesn’t actually work, should use LAMA/LAAC before this to achieve triple therapy with ICS, LABA, LAAC (same as COPD triple therapy))
6-11 years: increase LABA or LTRA
Anti IgE
Prednisone
15
Q
What is the natural progression of COPD
A
40s - Chronic productive cough, wheezing occasionally
50s - 1st acute chest illness
60s - Dyspnea on exertion, increasing sputum, more frequent exacerbations
Late Stage- Hypoxemia with cyanosis, polycythemia, hypercapnia (morning headache), cor pulmonale, weight loss
16
Q
COPD definition
A
- progressive and irreversible condition of the lung characterized by chronic obstruction to airflow with many patients having periodic exacerbations, gas trapping, lung hyperinflation, and weight loss
- 2 subtypes: chronic bronchitis and emphysema (usually coexist to variable degrees)
- gradual decrease in FEV1 over time with episodes of acute exacerbations
17
Q
What are some potential complications of COPD
A
- Polycythemia 2° to hypoxemia
- Chronic hypoxemia
- Pulmonary HTN from vasoconstriction
- Cor pulmonale
- Pneumothorax due to rupture of emphysematous bullae
- Depression
- Bacterial infections
18
Q
What are the clinical features of chronic bronchitis
A
Defined clinically
Productive cough on most days for at least 3 consecutive months in 2 successive years
Obstruction is due to narrowing of the airway lumen by mucosal thickening and excess mucous
19
Q
What are the pathological features of emphysema
A
Defined pathologically
Dilation and destruction of air spaces distal to the terminal bronchiole without obvious fibrosis
Decreased elastic recoil of lung parenchyma causes decreased expiratory driving pressure, airway collapse and air trapping
20
Q
What are 2 types of emphysema
A
1) Centriacinar (respiratory bronchiole) - typical form seen in smokers, primarily affects upper lung zones
2) Panacinar (all parts of acinus) - accounts for about 1% of emphysema cases, alpha 1 - antitrypsin deficiency, primarily affects lower lobes
21
Q
What should be a target O2 sat for CO2 retainers
A
On ABG, retainers have chronically elevated CO2 levels with a normal pH. Maintain O2 Sat between 88-92% to prevent Haldane effect, worsening V/Q mismatch, and decreased respiratory drive
22
Q
What is first line therapy for COPD
A
SMOKING CESSATION
23
Q
What is alpha 1 Antitrypsin deficiency
A
Inherited disorder of defective production of α1antitrypsin, a protein produced by hepatocytes.
Acts in the alveolar tissue by inhibiting the action of proteases from destroying alveolar tissue. When deficient, proteases can destroy lung alveoli resulting in emphysema
24
Q
COPD risk factors
A
• smoking is #1 risk factor
• others
■ environmental: air pollution, occupational exposure, exposure to wood smoke or other biomass fuel for cooking
■ treatable factors: α1-antitrypsin deficiency, bronchial hyperactivity
■ demographic factors: age, family history of atopy, male sex, history of childhood respiratory infections, low socioeconomic status
25
GOLD classification of severity of COPD
GOLD 1 Mild FEV1 ≥80% of predicted
GOLD 2 Moderate 50% ≤FEV1 <80% of predicted
GOLD 3 Severe 30% ≤ FEV1 <50% of predicted
GOLD 4 Very Severe FEV1 <30% of predicted
26
Symptoms and signs of "blue bloater" bronchitis
Chronic productive cough
Purulent sputum
Hemoptysis
Cyanosis (2º to hypoxemia and hypercapnia)
Peripheral edema from RVF (cor pulmonale)
Crackles, wheezes
Prolonged expiration if obstructive
Frequently obese
27
Bronchitis investigations
```
PFT:
Decreased FEV1
Decreased FEV1/FVC
Normal TLC
Decreased or Normal DLCO
```
CXR:
AP diameter normal
Increased bronchovascular markings
Enlarged heart with cor pulmonale
28
Signs and symptoms of "pink puffer" emphysema
Dyspnea (± exertion)
Minimal cough
Tachypnea
Decreased exercise tolerance
Pink skin
Pursed-lip breathing
Accessory muscle use
Cachectic appearance due to anorexia and increased work of breathing
Hyperinflation/barrel chest, hyperresonant percussion
Decreased breath sounds
Decreased diaphragmatic excursion
29
Emphysema investigations
```
PFT:
Decreased FEV1, Decreased FEV1/FVC
Increased TLC (hyperinflation)
Increased RV (gas trapping)
Increased DLCO
```
```
CXR:
Increased AP diameter
Flat hemidiaphragm (on lateral CXR)
Decreased heart shadow
Increased retrosternal space
Bullae
Decreased peripheral vascular markings
```
30
Systemic corticosteroids for acute COPD exacerbations
There is high-quality evidence to support treatment of exacerbaions of COPD with systemic corticosteroid by the oral or parenteral route in reducing the likelihood of treatment failure and relapse by 1 mo, shortening length of stay in hospital inpatients not requiring assisted ventilation in ICU and giving earlier improvement in lung function and symptoms. There is no evidence of benefit for parenteral treatment compared with oral treatment with corticosteroid on treatment failure, relapse or mortality. There is an increase in adverse drug effects with corticosteroid treatment, which is greater with parenteral administration compared with oral treatment.
31
What are COPD treatments that prolong survival
PROLONG SURVIVAL
Smoking Cessation - Nicotine replacement, bupropion, varenicline
Vaccination - Influenza, pneumococcal vaccine
Home Oxygen -
Prevents cor pulmonale and decreases mortality if used >15h/d
Indicated if
(1) PaO2 <55 mmHg or
(2) PaO2 <60 mmHg with cor pulmonale or polycythemia
32
What are COPD treatments that provide symptomatic relief with no mortality benefit
SYMPTOMATIC RELIEF (no mortality benefit)
- Bronchodilators (mainstay of current drug therapy, used in combination)
• Short-acting antcholinergics (e.g. ipratropium bromide) and short-acting β2-agonists (e.g. salbutamol, terbutaline)
SABAs: rapid onset but significant side effects at high doses (e.g. hypokalemia)
Short-acting anticholinergics more effective than SABAs with fewer side effects but slower onset; take regularly rather than PRN
• LABAs (e.g. salmeterol, formoterol, indacaterol) and long acting anticholinergics (e.g. tiotropium bromide, glycopyrronium bromide)
• More sustained effects for moderate to severe COPD
• Inhaled corticosteroid (ICS) + LABA combination (e.g. Advair®: fluticasone + salmeterol, Symbicort®: budesonide + formoterol)
• ICS/LABA increases effectiveness vs LABA alone
• Theophylline: weak bronchodilator; limited evidence to suggest combination with bronchodilator
• Side effects: nervous tremor, nausea/vomiting/diarrhea, tachycardia, arrhythmias, sleep changes
• PDE4 inhibitor: roflumilast (Daxas®) anti-inflammatory medication useful in COPD with chronic bronchitis, severe airflow obstruction, frequent exacerbations
- Corticosteroids
• ICS monotherapy has been shown to increase the incidence of pneumonia in COPD; ICS should only be used with a LABA in combination in patients with a history of exacerbations
• Oral steroids are important when treating exacerbations; chronic systemic glucocorticoids are generally not recommended due to unfavourable benefit to risk ratio
- Surgical
• Lung volume reduction surgery (resection of emphysematous parts of lung, associated with higher mortality if FEV1 <20%)
• lung transplant
- Other
• Patient education, eliminate respiratory irritants/allergens (occupational/environmental), exercise rehabilitation to improve physical endurance
33
Workup for patients with unexplained COPD exacerbation
Prevalence of PE in patients hospitalized for COPD exacerbation of unknown origin is 25%. Therefore, all patients presenting to hospital with COPD exacerbation without obvious cause require PE workup (leg dopplers or CTA – decision of which to use depends on pre-test probability of the patient).
34
COPD pharmacological management pyramid
Educations/Self-Management
PRN short acting bronchodilators
Long acting bronchodilators
Rehabilitation
ICS/LABA
O2
Surgery
35
NIPPV for treatment of respiratory failure due to COPD exacerbations
For patients in respiratory failure due to a COPD exacerbation, NPPV is effective in reducing treatment failure, mortality, and need for intubation when used as a first line treatment adjunct to UMC.
36
Acute exacerbations of COPD definition
■ sustained (>48 h) worsening of dyspnea, cough, or sputum production leading to an increased use of medications
■ in addition, defined as either purulent or non-purulent (to predict need for antibiotic therapy)
37
Acute exacerbations of COPD etiology
viral URTI, bacteria air pollution, CHF, PE, MI must be considered
38
COPD exacerbation management
■ ABCs, consider assisted ventilation if decreasing LOC or poor ABGs
■ O2: target 88-92% SaO2 for CO2 retainers
■ bronchodilators by MDI with spacer or nebulizer
◆ SABA + anticholinergic, e.g. salbutamol and ipratropium bromide via nebulizers × 3 back-toback q15min
■ systemic corticosteroids: IV solumedrol or oral prednisone
■ antibiotics for exacerbations with increased sputum production and at least one of the following:
◆ increased dyspnea or sputum purulence
◆ simple exacerbation (no risk factors): amoxicillin, 2nd or 3rd generation cephalosporin, macrolide, or TMP/SMX ◆ complicated exacerbation (one of: FEV1 ≤50% predicted, ≥4 exacerbations per year ischemic heart disease, home O2 use, chronic oral steroid use): fluoroquinolone or β-lactam + β-lactamase inhibitor (amoxicillin/clavulanate)
■ post exacerbation: rehabilitation with general conditioning to improve exercise tolerance
• ICU admission
■ for life-threatening exacerbations
■ ventilatory support
◆ non-invasive: NIPPV, BiPAP
◆ conventional mechanical ventilation
39
Duration of corticosteroid therapy for COPD exacerbation
5 d of oral corticosteroids is likely to be sufficient for treatment of adults with acute exacerbations of COPD, and this review suggests that the likelihood is low that shorter courses of systemic corticosteroids (of around five days) lead to worse outcomes than are seen with longer (10 to 14 d) courses.
40
COPD prognosis
• prognostic factors
■ level of dyspnea is the single best predictor
■ development of complications, e.g. hypoxemia or cor pulmonale
• 5 yr survival
■ FEV1 <1 L = 50%
■ FEV1 <0.75 L = 33%
• BODE index for risk of death in COPD
■ greater score = higher probability the patient will die from COPD; score can also be used to predict hospitalization
■ 10 point index consisting of four factors:
◆ Body mass index (BMI): <21 (+1 point)
◆ Obstruction (FEV1): 50-64% (+1), 36-49% (+2), <35% (+3)
◆ Dyspnea (MRC scale): walks slower than people of same age on level surface, stops occasionally (+1), stops at 100 yards or a few minutes on the level (+2), too breathless to leave house or breathless when dressing/undressing (+3)
◆ Exercise capacity (6 minute walk distance): 250-349 m (+1), 150-249 m (+2), <149 m (+3)
41
Bronchiectasis definition and common pathogens
* irreversible dilatation of airways due to inflammatory destruction of airway walls resulting from persistently infected mucus usually affects medium sized airways
* P. aeruginosa is the most common pathogen; S aureus, H. influenzae, and nontuberculous mycobacteria also common
42
What is Kartegener's syndrome
bronchiectasis, sinusitis, situs inversus
43
What types of obstructions can lead to bronchiectasis
Tumour
Foreign body
44
What types of infections can lead to post- infectious bronchiectasis (results in dilatation of bronchial walls)
```
Pneumonia
TB
Measles
Pertussis
Allergic bronchopulmonary aspergillosis
Non tuberculous mycobacterium (NTM)
```
45
What kinds of Impaired Defenses (leads to interference of drainage, chronic infections, and inflammation) can lead to bronchiectasis
```
Hypogammaglobinemia
CF
Defective leukocyte function
Ciliary dysfunction
Kartagener's syndrome
```
46
Bronchiectasis signs and symptoms
* chronic cough, purulent sputum (but 10-20% have dry cough), hemoptysis (can be massive), recurrent pneumonia, local crackles (inspiratory and expiratory), wheezes
* clubbing
* may be difficult to differentiate from chronic bronchitis
47
Bronchiectasis investigations
• PFTs: often demonstrate obstructive pattern but may be normal
• CXR
■ nonspecific: increased markings, linear atelectasis, loss of volume in affected areas
■ specific: “tram tracking” – parallel narrow lines radiating from hilum, cystic spaces, honeycomb like structures
• high-resolution thoracic CT (diagnostic, gold standard)
■ 87-97% sensitivity, 93-100% specificity
■ “signet ring”: dilated bronchi with thickened walls where diameter bronchus > diameter of accompanying artery
* sputum cultures (routine + AFB)
* serum Ig levels
* sweat chloride if cystic fibrosis suspected (upper zone predominant)
48
Bronchiectasis treatment
* vaccination: influenza and pneumococcal vaccination
* chest physiotherapy, breathing exercises, physical exercise
* antibiotics (oral, IV, inhaled): routinely used for mild exacerbations, driven by sputum sensitivity; macrolides may be used chronically for an anti-inflammatory effect
* inhaled antibiotics (tobramycin) used chronically to suppress Pseudomonas and reduce exacerbations
* mucolytics (e.g. hypertonic saline, N.B. DNAse only in CF)
* inhaled corticosteroids: decrease inflammation and improve FEV1; however, may increase risk of exacerbations
* oral corticosteroids for acute, major exacerbations
* pulmonary resection: in selected cases with focal bronchiectasis
49
Cystic fibrosis usual first presentation
Usually presents in childhood as recurrent lung infections that become persistent and chronic
50
Cystic fibrosis pathophysiology
• chloride transport dysfunction: thick secretions from exocrine glands (lung, pancreas, skin, reproductive organs) and blockage of secretory ducts
51
Cystic fibrosis clinical features
* results in severe lung disease, pancreatic insufficiency, diabetes, and azoospermia
* other manifestations: meconium ileus in infancy, distal ileal obstruction in adults, sinusitis, liver disease
```
• chronic lung infections
■ S. aureus: early
■ P. aeruginosa: most common
■ B. cepacia: worse prognosis but less common
■ Aspergillus fumigatus
```
52
Cystic fibrosis investigations
• Sweat chloride test
■ increased concentrations of NaCl and K+ ([Cl–] >60 mmol/L suggests diagnosis in children)
■ heterozygotes have normal sweat tests (and no symptoms)
• PFTs
■ early: airflow limitation in small airways
■ late: severe airflow obstruction, hyperinflation, gas trapping, decreased DLCO (very late)
• ABGs
■ hypoxemia, hypercapnia later in disease with eventual respiratory failure and cor pulmonale
• CXR
■ hyperinflation, increased pulmonary markings (especially upper lobes)
53
Cystic fibrosis treatment
* chest physiotherapy and postural drainage
* pancreatic enzyme replacements, high calorie diet
* bronchodilators (salbutamol ± ipratropium bromide)
* inhaled mucolytic (reduces mucus viscosity), hypertonic saline DNase
* inhaled antibiotics (tobramycin, colistin, aztreonam)
* antibiotics (eg ciprofloxacin)
* CFTR potentiators (e.g Ivacaftor)
* lung transplant
54
Cystic fibrosis prognosis
* depends on: infections (cepacia colonization), FEV1, acute pulmonary exacerbations, lung transplant vs. non-lung transplant
* female gender and low socioeconomic class have greater risk of early death
55
ILD upper lung disease differential
FASSTEN
Farmer’s lung (hypersensitivity pneumonitis)
Ankylosing spondylitis
Sarcoidosis
Silicosis
TB
Eosinophilic granuloma (Langerhans-cell histiocytosis)
Neurofibromatosis
56
ILD lower lung disease differential
BAD RASH
Bronchiolitis obliterans with organizing pneumonia (BOOP)
Asbestosis
Drugs (nitrofurantoin, hydralazine, INH, amiodarone, many chemo drugs)
Rheumatologic disease
Aspiration
Scleroderma
Hamman Rich (acute interstitial pneumonia) and IPF
57
Interstitial lung disease definition
• a group of disorders which cause progressive scarring of lung tissue and impair lung function and gas exchange
58
Interstitial lung disease pathophysiology
• inflammatory and/or fibrosing process in the alveolar walls → distortion and destruction of normal alveoli and microvasculature
• typically associated with
■ lung restriction (decrease in TLC and VC)
■ decreased lung compliance (increased or normal FEV1/FVC)
■ impaired diffusion (decreased DLCO)
■ hypoxemia due to V/Q mismatch (usually without hypercapnia until end stage)
■ pulmonary HTN and cor pulmonale occur with advanced disease secondary to hypoxemia and blood vessel destruction
59
Unknown etiologies of interstitial lung disease
1. Idiopathic interstitial pneumonias
UIP (usual interstitial pneumonia)
NSIP (non-specific interstitial pneumonia)
LIP (lymphoctic interstitial pneumonia)
COP (cryptogenic organizing pneumonia ex BOOP)
DIP (desquamative interstitial pneumonia)
IPPFE (idiopathic pleuroparenchymal fibroelastosis)
AFOP (acute fibrinous and organizing penumonia)
2. Sarcoidosis
3. Langerhans - cell histiocytosis (eosinophilic granuloma)
4. Lymphangioleiomyomatosis
60
Known etiologies of interstitial lung disease
1. ILD associated with systemic rheumatic disorders
- Scleroderma
- Rheumatoid arthritis
- SLE
- Polymyositis/dermatomyositis
- Anti-synthetase dynromes
- Mixed connective tissue disease
2. Environmental/occupation associated ILD
- Hypersensitivity pneumonitis (usually organic antigen)
Farmer's lung, air conditioner/humidifier lung, bird breeder's lung
- Pneumoconioses (inorganic dust)
Silicosis, asbestosis, coal worker's pneumoconiosis, chronic beryllium disease
- Pneumonitis from gases/fumes/vapour
3. ILD associated with drugs or treatments
- Antibiotics (nitrofurantoin)
- Anti-inflammatory agents (methotrexate)
- Cardiovascular drugs (amiodarone)
- Antineoplastic agents (chemo)
- Illicit drugs (ex. crack lung, talc granulomatosis)
- Radiation
4. ILD associated with pulmonary vasculitis
- Granulomatosis with polyangiitis (GPA)
- Goodpasture's syndrome
- Idiopathic pulmonary hemosiderosis
5. Inherited disorders
- Familial IPF
- Telomerase mutations
Neurofibromatosis, tuberous sclerosis, Gaucher's disease
- Alveolar filling disorders
Chronic eosinophilic pneumonia, pulmonary alveolar proteinosis
61
ILD signs and symptoms
• dyspnea, especially on exertion
• nonproductive cough
• crackles (dry, fine, end-inspiratory)
• clubbing (especially in IPF and asbestosis)
• features of cor pulmonale
• note that signs and symptoms vary with underlying disease process
■ e.g. sarcoidosis is seldom associated with crackles and clubbing
62
ILD investigations
• CXR/high resolution CT
■ usually decreased lung volumes
■ reticular, nodular, or reticulonodular pattern (nodular <3 mm)
■ hilar/mediastinal adenopathy (bilateral especially in sarcoidosis)
The CXR can be normal in up to 15% of patients with interstitial lung disease
• PFTs
■ restrictive pattern: decreased lung volumes and compliance
■ normal or increased FEV1/FVC (>70-80%), e.g. flow rates are often normal or high when corrected for absolute lung volume
■ DLCO decreased due to V/Q mismatch (less surface area for gas exchange ± pulmonary vascular disease)
• ABGs
■ hypoxemia and respiratory alkalosis may be present with progression of disease
• other
■ bronchoscopy, bronchoalveolar lavage, lung biopsy
■ ESR, ANA (lupus), RF (RA), serum-precipitating antibodies to inhaled organic antigens (hypersensitivity pneumonitis), c-ANCA (GPA), anti-GBM (Goodpasture’s)
63
Idiopathic pulmonary fibrosis definition
* pulmonary fibrosis of unknown cause with usual interstitial pneumonia (UIP) histology (found on biopsy or inferred from CT)
* a progressive, irreversible condition
* DDx: NSIP, COP, desquamative interstitial pneumonitis (DIP), lymphocytic interstitial pneumonitis (LIP), Sjögren’s disease
64
IPF signs and symptoms
* commonly presents over age 50, incidence rises with age; males > females
* dyspnea on exertion, nonproductive cough, constitutional symptoms, late inspiratory fine crackles at lung bases, clubbing
65
IPF investigations
* labs (nonspecific, autoimmune serology usually negative)
* CXR: reticular or reticulonodular pattern with lower lung predominance; often see honeycombing in advanced disease
* high resolution CT: lower zone peripheral reticular markings, traction bronchiectasis, honeycombing; ground glass, consolidation, or nodules should not be prominent in IPF
* biopsy: rarely for UIP as honeycombing usually makes radiologic diagnosis possible
66
IPF treatment
* O2
* pirfenidone and nintedanib can slow disease progression
* lung transplantation for advanced disease
* mean survival of 3-5 yr after diagnosis
67
Sarcoidosis definition
* idiopathic non-infectious granulomatous multi-system disease with lung involvement in 90%
* characterized pathologically by non-caseating granulomas
* numerous HLA antigens have been shown to play a role and familial sarcoidosis is now recognized
68
Sarcoidosis epidemiology
* typically affects young and middle-aged patients
| * higher incidence among people of African descent and from northern latitudes e.g. Scandinavia, Canada
69
Sarcoidosis signs and symptoms
* asymptomatic cough, dyspnea, fever, arthralgia, malaise, erythema nodosum, chest pain
* chest exam often normal
• common extrapulmonary manifestations
■ cardiac (arrhythmias, sudden death)
■ eye involvement (anterior or posterior uveitis)
■ skin involvement (skin papules, erythema nodosum, lupus pernio)
■ peripheral lymphadenopathy
■ arthralgia
■ hepatomegaly ± splenomegaly
• less common extra-pulmonary manifestations involve bone, CNS, kidney
• two acute sarcoid syndromes
■ Lofgren’s syndrome: fever, erythema nodosum, bilateral hilar lymphadenopathy, arthralgias
■ Heerfordt-Waldenstrom syndrome: fever, parotid enlargement, anterior uveitis, facial nerve palsy
70
What is the most common presentation of sarcoidosis
asymptomatic CXR finding
71
Sarcoidosis investigations
* CBC (cytopenias from spleen or marrow involvement)
* serum electrolytes, creatinine, liver enzymes, calcium (hypercalcemia/hypercalciuria due to vitamin D activation by granulomas)
* hypergammaglobulinemia, occasionally RF positive
* elevated serum ACE (non-specific and non-sensitive)
* CXR: predominantly nodular opacities especially in upper lung zones ± hilar adenopathy
* PFTs: normal, obstructive pattern, restrictive pattern with normal flow rates and decreased DLCO, or mixed obstructive/restrictive pattern
* ECG: to rule out conduction abnormalities
* slit-lamp eye exam: to rule out uveitis
72
Sarcoidosis diagnosis
• biopsy
■ transbronchial lung biopsy transbronchial lymph node aspiration, endobronchial ultrasound guided surgical (EBUS) biopsy, or mediastinoscopic lymph node biopsy for granulomas
■ in ~75% of cases, transbronchial biopsy shows granulomas in the parenchyma even if the CXR is normal
73
Hilar lymphadenopathy presentation and differential
Hilar adenopathy refers to enlargement of mediastinal lymph nodes which is most often seen by standard CXR as spherical/ellipsoidal and/or calcified nodes. If unilateral - think neoplasia, TB, or sarcoid. If bilateral - think sarcoid or lymphoma
74
Sarcoidosis staging
• radiographic, based on CXR
■ Stage 0: normal radiograph
■ Stage I: bilateral hilar lymphadenopathy ±paratracheal lymphadenopathy
■ Stage II: bilateral hilar lymphadenopathy with pulmonary infiltration
■ Stage III: pulmonary infiltration alone (reticulonodular pattern or nodular pattern) ■
Stage IV: pulmonary fibrosis (honeycombing)
75
Role for corticosteroids in pulmonary sarcoidosis
Oral steroids improve CXR findings and global scores of CXR, symptoms, and spirometry over 3-24 mo, but do not improve lung function or modify disease course. Oral steroids may be of benefit for patients with Stage 2 and 3 disease.
76
Sarcoidosis treatment
* steroids for symptoms, declining lung function, hypercalcemia, or involvement of eye, CNS, kidney, or heart (not for abnormal CXR alone)
* methotrexate or other immunosuppressives occasionally used
77
Sarcoidosis prognosis
* 85% of stage I resolve spontaneously
* 50% of stage II resolve spontaneously
* approximately 10% mortality secondary to progressive fibrosis of lung parenchyma
78
Calcified diaphragmatic plaques are highly suggestive of what condition
asbestosis, especially if bilateral
79
Hypersensitivity pneumonitis pathophysiology
* also known as extrinsic allergic alveolitis
* non-IgE mediated inflammation of lung parenchyma (acute, subacute, and chronic forms) Type 4 hypersensitivity reaction
* caused by sensitization to inhaled agents, usually organic dust
* pathology: airway-centred, poorly formed granulomas and lymphocytic inflammation
• exposure usually related to occupation or hobby
■ Farmer’s Lung (Thermophilic actinomycetes)
■ Bird Breeder’s/Bird Fancier’s Lung (immune response to bird IgA)
■ Humidifier Lung (Aureobasidium pullulans)
■ Sauna Taker’s Lung (Aureobasidium spp.)
80
CXR fibrosis patterns for asbestos, silicosis and coal
* Asbestosis: lower > upper lobes
* Silicosis: upper > lower lobes
* Coal: upper > lower lobes
81
Hypersensitivity pneumonitis signs and symptoms
• acute presentation: (4-6 h after exposure)
■ dyspnea, cough, fever, chills, malaise (lasting 18-24 h)
■ CXR: diffuse infiltrates
■ type III (immune complex) reaction
• subacute presentation: more insidious onset than acute presentation
• chronic presentation
■ insidious onset
■ dyspnea, cough, malaise, anorexia, weight loss
■ PFTs: progressively restrictive
■ CXR: predominantly upper lobe reticulonodular pattern
• in both acute and chronic reactions, serum precipitins may be detectable (neither sensitive nor specific)
82
Hypersensitivity pneumonitis treatment
* early diagnosis: avoidance of further exposure is critical as chronic changes are irreversible
* systemic corticosteroids can relieve symptoms and speed resolution
83
Pneuomoconioses definition and treatment
* reaction to inhaled inorganic dusts 0.5-5 µm in size
* no effective treatment, therefore key is exposure prevention through the use of protective equipment
* smoking cessation, annual influenza and pneumococcal vaccination rehabilitation, lung transplant for endstage disease
84
Types of pneumoconioses
Asbestosis, silicosis, Coal Worker’s Pneumoconiosis (CWP)
85
Asbestosis etiology
Exposure risks: insulation, shipyard, construction, brake linings, pipe fitters plumbers Slowly progressive diffuse interstitial fibrosis induced by inhaled asbestos fibres Usually requires >10-20 yr of exposure Latency period: 20-30 yr
86
Asbestosis signs and symptoms
Insidious onset
Dyspnea
Cough: paroxysmal, non-productive
Clubbing (much more likely in asbestosis than silicosis or CWP)
87
Asbestosis investigations
CXR
Lower > upper lobe
Reticulonodular pattern, may develop IPF-like honeycombing
Asbestos exposure can also cause pleural and diaphragmatic plaques (± calcification), pleural effusion, round atelectasis
Microscopic examination reveals ferruginous bodies: yellow-brown rod-shaped structures which represent asbestos fibres coated in macrophages
88
Asbestosis complications
Asbestos exposure increases risk of bronchogenic CA and malignant mesothelioma Risk of lung cancer dramatically increased for smokers
89
Silicosis etiology
At risk population: sandblasters, rock miners, stone cutters, quarry and highway workers Generally requires >20 yr exposure; may develop with much shorter but heavier exposure
90
Silicosis signs and symptoms
Dyspnea, cough, wheezing
91
Silicosis investigations
CXR Upper > lower lobe Early: nodular disease (simple pneumoconiosis), lung function usually normal Late: nodules coalesce into masses (progressive massive fibrosis) Possible hilar lymph node enlargement (frequently calcified), especially “egg shell” calcification
92
Silicosis complications
Mycobacterial infection (ex. TB)
93
CWP etiology
At risk population: coal workers, graphite workers Coal and silca, coal is less fibrogenic than silica
94
CWP signs and symptoms
Simple CWP No signs or symptoms, usually normal lung function Complicated CWP (also known as progressive massive fibrosis) Dyspnea Course: few patients progress to complicated CWP
95
CWP investigations
Simple CWP
CXR: multiple nodular opacities, mostly upper lobe Pathologic hallmark is coal macule
Complicated CWP
CXR: opacities larger and coalesce
96
CWP complications
Caplan's syndrome: Rheumatoid arthritis and CWP present as larger nodules
97
Interstitial lung disease associated with drugs or other treatments
* antineoplastic agents: bleomycin, mitomycin, busulfan, cyclophosphamide, methotrexate, chlorambucil, BCNU (carmustine)
* antibiotics: nitrofurantoin, penicillin, sulfonamide
* cardiovascular drugs: amiodarone, tocainide
* anti-inflammatory agents: methotrexate, penicillamine
* gold salts
* illicit drugs (heroin, methadone)
* rituximab, anti-TNF-α agents (infliximab, etanercept, adalimumab)
Radiation-Induced
• early pneumonitis: approximately 6 wk post-exposure
• late fibrosis: 6-12 mo post-exposure
• infiltrates conform to the shape of the radiation field
98
Pulmonary hypertension definition
mean pulmonary arterial pressure >25 mmHg at rest and >30 mmHg with exercise, or a systolic pulmonary artery pressure of >40 mmHg at rest
99
What are the WHO classifications of pulmonary hypertension?
1. Pulmonary arterial hypertension
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung disease and/or hypoxia
4. Chronic thromboembolic pulmonary hypertension (CTEPH)
5. Pulmonary hypertension with unclear multifactorial mechanisms
100
What are some causes of pulmonary arterial hypertension
Idiopathic Collagen vascular disease (scleroderma, SLE, RA)
Congenital systemic-to-pulmonary shunts (Eisenmenger syndrome)
Persistent pulmonary hypertension of the newborn (PPHN)
Portopulmonary HTN
HIV infection
Drugs and toxins (e.g. anorexigens)
Pulmonary veno-occlusive disease
Schistosomiasis
Pulmonary capillary hemangiomatosis
101
Pulmonary arterial hypertension treatment options
CCB in occasional patients with vasoreactivity (now used infrequently) advanced therapy often needed
The latter includes: prostanoids, endothelin receptor antagonists, PDE5 inhibitors
Lung transplantation
102
What are some causes of pulmonary hypertension due to left heart disease
Left-sided atrial or ventricular heart disease (e.g. LV dysfunction)
Left-sided valvular heart disease (e.g. aortic stenosis, mitral stenosis)
Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies
103
Pul HTN due to left heart disease treatment
Treat underlying cause
104
Pulmonary hypertension due to lung disease and/or hypoxia causes
Parenchymal lung disease (COPD, interstitial fibrosis, cystic fibrosis)
Chronic alveolar hypoxia (chronic high altitude, alveolar hypoventilation disorders, sleep-disordered breathing)
105
Pulmonary hypertension due to lung disease and/or hypoxia treatment
Treat underlying cause of hypoxia and correct with supplemental oxygen (proven mortality benefit)
106
Chronic thromboembolic pulmonary hypertension (CTEPH) causes
Thromboembolic obstruction of proximal pulmonary arteries
Obstruction of distal pulmonary arteries – PE (thrombus, foreign material, tumour, in situ thrombosis)
107
Chronic thromboembolic pulmonary hypertension (CTEPH) treatment
Anticoagulation, thromboendarterectomy
108
Pulmonary hypertension with unclear multifactorial mechanisms causes
Hematologic disorders (e.g. sickle cell)
Systemic disorders (e.g. sarcoidosis)
Metabolic disorders
Extrinsic compression of central pulmonary veins (tumour, adenopathy, fibrosing mediastinitis)
Chronic hemolytic anemia
Segmental pulmonary hypertension
109
Pulmonary hypertension with unclear multifactorial mechanisms treatment
Treat underlying cause
110
What treatment should be considered in every patient with pulmonary hypertension
Oxygen therapy
Exercise
Consider anticoagulation
111
What is the definition of idiopathic pulmonary arterial hypertension
* pulmonary HTN in the absence of a demonstrable cause
* histology includes medial hypertrophy, intimal fibrosis and plexiform arteriopathy
```
• exclude:
■ left-sided cardiac valvular disease
■ myocardial disease
■ congenital heart disease
■ any clinically significant parenchymal lung disease
■ systemic connective-tissue disease
■ chronic thromboembolic disease
```
112
Idiopathic pulmonary arterial hypertension etiology
* usually presents in young females (20-40 yr); mean age of diagnosis is 36 yr
* most cases are sporadic; familial predisposition in 10% of cases, some linked to mutations in BMPR2
* may be associated with the use of anorexic drugs (e.g. Aminorex®, Fenfluramine®), amphetamines, and cocaine
113
What are the guidelines for vasodilator use in pulmonary arterial hypertension
* Patients with IPAH that respond to vasodilators acutely, have an improved survival with long-term use of CCBs
* Vasoreactivity testing: short-acting agent such as IV epoprostenol, IV adenosine, or inhaled NO
* Positive vasodilator response: mean PAP fall of at least 10 mmHg to ≤40 mmHg with an increased or unchanged cardiac output (European Society of Cardiology)
* Positive vasodilator response: should be considered as candidate for trial of oral CCB therapy
114
Symptoms and signs of pulmonary hypertension
Symptoms - dyspnea, fatigue, retrosternal chest pain, syncope, symptoms of underlying disease
Signs -
loud, palpable S2
RV heave
right sided S4 (due to RVH)
systolic murmur (tricuspid regurgitation)
If RV failure: right sided S3, increased JVP, positive HJR, peripheral edema, TR
Reynaud’s phenomenon
115
What is Virchow's triad
* Venous stasis
* Endothelial cell damage
* Hypercoagulable states
116
Pulmonary hypertension investigations
• CXR: enlarged central pulmonary arteries, cardiac changes due to RV enlargement (filling of retrosternal air space)
• ECG
■ RVH/right-sided strain
* 2-D echo doppler assessment of right ventricular systolic pressure
* cardiac catheterization: direct measurement of pulmonary artery pressures (necessary to confirm diagnosis)
* PFTs to assess for underlying lung disease: DLCO usually reduced; volumes and flows normal
* CT angiogram to assess lung parenchyma and possible PE
* V/Q scan ± pulmonary angiogram to rule out thromboembolic disease
* serology: ANA positive in 30% of patients with primary pulmonary HTN; other serologic markers can be used in the appropriate clinical setting
117
Pulmonary hypertension prognosis
* 2-3 yr mean survival from time of diagnosis
| * survival decreases to approximately 1 yr if severe pulmonary HTN or right-heart failure
118
Pulmonary embolism definition
• lodging of a blood clot in the pulmonary arterial tree with subsequent increase in pulmonary vascular resistance, impaired V/Q matching, and possibly reduced pulmonary blood flow
119
Pulmonary embolism pathophysiology
* one of the most common causes of preventable death in the hospital
* proximal leg thrombi (popliteal, femoral, or iliac veins) are the source of most clinically recognized pulmonary emboli
* thrombi often start in calf, but must propagate into proximal veins to create a sufficiently large thrombus for a clinically significant PE
* fewer than 30% of patients have clinical evidence of DVT (e.g. leg swelling, pain, or tenderness)
* always suspect PE if patient develops fever, sudden dyspnea, chest pain, or collapse 1-2 wk after surgery
120
PE risk factors
• stasis
■ immobilization: paralysis, stroke, bed rest, prolonged sitting during travel, immobilization of an extremity after fracture
■ obesity, CHF
■ chronic venous insufficiency
• endothelial cell damage
■ post-operative injury, trauma
• hypercoagulable states
■ underlying malignancy (particularly adenocarcinoma)
■ cancer treatment (chemotherapy, hormonal)
■ exogenous estrogen administration (OCP, HRT)
■ pregnancy, post-partum
■ prior history of DVT/PE, family history
■ nephrotic syndrome
■ coagulopathies: Factor V Leiden, Prothrombin 20210A variant, inherited deficiencies of antithrombin/protein C/protein S, antiphospholipid antibody, hyperhomocysteinemia, increased Factor VIII levels, and myeloproliferative disease
• increasing age
121
What is the gold standard investigation for PE
Pulmonary Angiogram (harder to perform than CT though)
122
What are ECG changes that can be seen with PE
Sinus tachycardia most common
May see non-specific ST segment and T wave changes
RV strain, RAD, RBBB, S1-Q3-T3 with massive embolization
123
What are CXR signs that can be seen with PE
Frequently normal; no specific features
Atelectasis (subsegmental), elevation of a hemidiaphragm
Pleural effusion: usually small
Hampton’s hump: cone-shaped area of peripheral opacification representing infarction
Westermark’s sign: dilated proximal pulmonary artery with distal oligemia/decreased vascular markings (difficult to assess without prior films)
Dilatation of proximal PA: rare
124
What is the Well's criteria for PE
Hemoptysis 1.0
Malignancy 1.0
Previous PE/DVT 1.5
Immobilization or surgery in previous 4 wk 1.5
Tachycardia HR >100 beats/min 1.5
Clinical signs of DVT 3.0
No more likely alternative diagnosis 3.0 (using H&P, CXR, ECG)
0-4 unlikely
5+ likely
125
What are the benefits, indications and contraindications of a V/Q scan
Very sensitive but low specificity
Order scan if:
- CXR normal, no COPD
- Contraindication to CT (contrast allergy, renal dysfunction, pregnancy)
Avoid V/Q scan if:
- CXR abnormal or COPD
- Inpatient
- Suspect massive PE
Results:
Normal: excludes the diagnosis of PE
High probability: most likely means PE present, unless pre test probability is low
60% of V/Q scans are nondiagnostic
126
Role of echocardiogram in PE
Useful to assess massive or chronic PE
Not routinely done
127
Role of ABG in PE
No diagnostic use in PE (insensitive and nonspecific)
May show respiratory alkalosis (due to hyperventilation)
128
PERC rule
* Age less than 50 yr
* Heart rate less than 100 bpm
* Oxyhemoglobin saturation 95 percent
* No hemoptysis
* No prior DVT or PE
* No unilateral leg swelling
* No estrogen use
* No surgery or trauma requiring hospitalization within the past 4 wk
129
Evaluation of a suspected PE
Low clinical probability of embolism
D-dimer (+ve) → CT scan (+ve) → ruled in
(–ve) → ruled out
Intermediate or high probability
CT scan (–ve) → ruled out
(+ve) → ruled in
Notes
• Use D-dimers only if low clinical probability, otherwise, go straight to CT
• If using V/Q scans (CT contrast allergy or renal failure): - Negative V/Q scan rules out the diagnosis
- High probability V/Q scan only rules in the diagnosis if have high clinical suspicion
- Inconclusive V/Q scan requires leg U/S to look for DVT or CT
130
PE treatment
* admit for observation (stable patients with DVT only may be sent home on LMWH)
* oxygen: supplemental O2 if hypoxemic or short of breath
* pain relief: analgesics if chest pain – narcotics or acetaminophen
■ acute anticoagulation:
therapeutic-dose SC LMWH or rivaroxaban or IV heparin (only if concern for bleeding risk) – start ASAP
■ anticoagulation stops clot propagation, prevents new clots and allows endogenous fibrinolytic system to dissolve existing thromboemboli over months - get baseline CBC, INR, aPTT ± renal function ± liver function
■ for SC LMWH: dalteparin 200 U/kg once daily, enoxaparin 1 mg/kg bid or 1.5mg/kg once daily, or tinzaparin 175 U/kg once daily – no lab monitoring – avoid or reduce dose in renal dysfunction
■ for IV heparin: bolus of 75 U/kg (usually 5,000 U) followed by infusion starting at 20 U/kg/h – aim for aPTT 2-3x control
■ rivaroxaban is accepted alternative for acute PE
• long-term anticoagulation
■ warfarin : start the same day as LMWH/heparin – overlap warfarin with LMWH/heparin for at least 5 d and until INR in target range of 2-3 for at least 2 d
■ LMWH instead of warfarin for pregnancy, active cancer, or high bleeding risk patients
■ direct thrombin inhibitors: can treat from outset with rivaroxaban; dabigatran has been shown to have lower bleeding risk than warfarin; no monitoring required, however agents not reversible, so avoid if bleeding concerns
• IV thrombolytic therapy
■ if patient has massive PE (hypotension or clinical right heart failure) and no contraindications
■ hastens resolution of PE but may not improve survival or long-term outcome and doubles risk of major bleeding
• interventional thrombolytic therapy
■ massive PE may be treated with catheter-directed thrombolysis by an interventional radiologist
■ catheter-directed thrombolysis is not recommended over systemic thrombolysis
• IVC filter: only if recent proximal DVT + absolute contraindication to anticoagulation
• duration of long-term anticoagulation: individualized, however generally
■ if reversible cause for PE (surgery, injury, pregnancy, etc.): 3-6 mo
■ if PE unprovoked: 6 mo to indefinite
■ if ongoing major risk factor (active cancer, antiphospholipid antibody, etc.): indefinite
131
The use of unfractionated heparin in patients with PE should be limited to
* Patients with severe renal dysfunction (CrCl <30 ml/min) in whom LMWH and novel oral anticoagulation should be avoided
* Patients at elevated risk of bleeding that may need rapid reversal of anticoagulation
* Patients who receive thrombolytic therapy
132
How long should thromboprophylaxis be used for in hospital admissions
• continue at least until discharge or recommend extending for 35 d post-operatively, if major orthopedic surgery
133
Results of extended use of Dabigatron, Warfarin or placebo in VTE
Dabigatran appears to be non-inferior to warfarin in the prevention of VTE recurrence.
Dabigatran is associated with a lower risk of major or clinicaly relevant bleed than warfarin, but greater than placebo.
134
VTE prophylaxis for low thrombosis risk patients (surgery <30 minutes, fully mobile)
No specific prophylaxis, frequent ambulation
135
VTE prophylaxis for moderate thrombosis risk patients (Most general, gynecologic, urologic surgery, sick medical patients)
LMWH
Low dose unfractionated heparin
Fondaparinux
136
VTE prophylaxis for high thrombosis risk patients (arthroplasty, hip fracture surgery, major trauma, spinal cord injury)
```
LMWH
Fondaparinux
Low dose unfractionated heparin
Warfarin (INR 2-3)
Dabigatran Apixaban Rivaroxaban
```
137
VTE prophylaxis for high bleeding risk patients (neurosurgery, intracranial bleed, active bleeding)
TED stockings
Pneumatic compression device
LMWH or low dose unfractionated heparin when bleeding risk decreases
138
Types of pulmonary vasculitis
Granulomatosis with Polyangiitis (GPA, previuosly Wegener's Granulomatosis)
Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss)
Anti-GBM Disease (Goodpasture's)
SLE, RA, Scleroderma
139
Definition of Granulomatosis with Polyangiitis (GPA, previuosly Wegener's Granulomatosis)
Systemic vasculitis of medium and small arteries
140
Definition of Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss)
Multisystem disorder characterized by allergic rhinitis, asthma and prominent peripheral eosinophilia
141
Definition of Anti-GBM Disease (Goodpasture's)
A disorder characterized by diffuse alveolar hemorrhage and glomerulonephritis caused by anti-GBM antibodies, which cross-react with basement membranes of the kidney and lung
142
Granulomatosis with Polyangiitis (GPA, previuosly Wegener's Granulomatosis) pulmonary features
Necrotizing granulomatous lesions of the upper and lower respiratory tract
143
Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss) pulmonary features
asthma infiltrates
144
Anti-GBM Disease (Goodpasture's) pulmonary features
Hemoptysis
| May follow an influenza infection
145
Granulomatosis with Polyangiitis (GPA, previuosly Wegener's Granulomatosis) extrapulmonary features
Focal necrotizing lesions of arteries and veins; crescentic glomerulonephritis
146
Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss) extrapulmonary features
Life-threatening systemic vasculitis involving the lungs, pericardium and heart, kidneys, skin, and PNS (mononeuritis multiplex)
147
Anti-GBM Disease (Goodpasture's) extrapulmonary features
Anemia
148
Granulomatosis with Polyangiitis (GPA, previuosly Wegener's Granulomatosis) investigations
CXR: nodules, cavities, and alveolar opacities
c-ANCA
Tissue confirmation
149
Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss) investigations
Peripheral eosinophilia is the most common finding
p-ANCA may be positive
Biopsy involved tissue
150
Anti-GBM Disease (Goodpasture's) investigations
CXR: may see alveolar infiltrates if hemorrhage is profuse
ELISA test with anti-GBM antibodies
Renal biopsy/indirect immunofluorescence shows linear staining
151
Granulomatosis with Polyangiitis (GPA, previuosly Wegener's Granulomatosis) treatment
Corticosteroids and cyclophosphamide or rituximab
152
Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss) treatment
Corticosteroids
153
Anti-GBM Disease (Goodpasture's) treatment
Acutely: corticosteroids, plasmapheresis, immunosuppressive therapy
Severe cases: bilateral nephrectomy
154
What is the most common collagen vascular disease affecting the lung
Scleroderma
155
What is the definition of the mediastinum?
* mediastinum: bound by the thoracic inlet, diaphragm sternum, vertebral bodies, and the pleura
* can be broken down into 3 compartments: anterior, middle, and posterior
Anterior: sternum to pericardium and great vessels. Includes: thymus, extrapericardial aorta and branches, great veins, lymphatic tissues
Middle: pericardium (anteriorly) posterior pericardial reflection, diaphragm, thoracc inlet. Includes: heart, intrapericaridal great vessels, pericardium, trachea
Posterior: posterior pericardial reflection, posterior border of vertebral bodies, first rib to the diaphragm. Includes: esophagus, vagus nerve, thoracic duc sympathetic chain, azygous venous system
156
What is the differential diagnosis of an anterior compartment mediastinal mass?
Thymoma
Thyroid enlargement (goitre)
Teratoma
Tumours (lymphoma, parathyroid, esophageal, angiomatous)
157
What is the differential diagnosis of a middle compartment mediastinal mass?
pericardial cyst, bronchogenic cyst/tumour, lymphoma, lymph node enlargement, aortic aneurysm
158
What is the differential diagnosis of a posterior compartment mediastinal mass?
neurogenic tumours, meningocele, enteric cysts, lymphoma, diaphragmatic hernias, esophageal tumour, aortic aneurysm
159
What are the signs and symptoms of a mediastinal mass?
* 50% asymptomatic (mainly benign); when symptomatic, 50% are malignant
* chest pain, cough, dyspnea, recurrent respiratory infections
* hoarseness, dysphagia, Horner’s syndrome, facial/upper extremity edema (SVC compression)
* paraneoplastic syndromes (e.g. myasthenia gravis [thymomas])
160
Mediastinal mass investigations
* CXR (compare to previous)
* CT with contrast (anatomic location, density, relation to mediastinal vascular structures)
* MRI: specifically indicated in the evaluation of neurogenic tumours
* U/S (best for assessment of structures in close proximity to the heart and pericardium)
* radionuclide scanning: 131I (for thyroid), gallium (for lymphoma)
* biochemical studies: thyroid function, serum calcium, phosphate, PTH, AFP, β hCG
* biopsy (mediastinoscopy, percutaneous needle aspiration)
161
Mediastinal mass management
* excision if symptomatic enlarging benign masses or concerns of malignancy
* resect bronchogenic cysts and localized neurogenic tumours via minimally invasive video assisted procedures
* exploration via sternotomy or thoracotomy
* diagnostic biopsy rather than major operation if mass is likely to be a lymphoma, germ cell tumour, or unresectable invasive malignancy
* ± post operative radiotherapy/chemotherapy if malignant
162
What is the most common cause of mediastinitis?
post-operative complications of cardiovascular or thoracic surgical procedures
163
Signs and symptoms of acute mediastinitis
■ fever, substernal pain
■ pneumomediastinum, mediastinal compression
■ Hamman’s sign (auscultatory “crunch” during cardiac systole)
164
Acute Mediastinitis treatment
■ antibiotics (IV vancomycin + 3rd gen cephalosporin), drainage, ± surgical closure of perforation
165
Acute mediastinitis etiologies
■ complication of endoscopy (e.g. esophageal perforation providing entry point for infecton)
■ esophageal or cardiac surgery
■ tumour necrosis
166
Chronic mediastinitis etiologies
• usually granulomatous process or fibrosis related to previous infection (e.g. histoplasmosis, TB, sarcoidosis, syphilis)
167
Definition pleural effusion
• excess amount of fluid in the pleural space (normally up to 25 mL)
168
Pleural effusion etiology
• disruption of normal equilibrium between pleural fluid formation/entry and/or pleural fluid absorption/exit
• pleural effusions are classified as transudative or exudative
■ distinguish clinically using Light’s Criteria, which has a sensitivity of 98% and specificity of 83% for identifying exudative pleural effusions
169
What is Light's Criteria and Modified Light's Criteria
All criteria for transudate must be fulfilled to be considered a transudative effusion. If any one of the criteria for exudates is met – it is an exudate
Light's listed first, then modified Light's
Protein – Pleural/Serum >0.5 >0.5
LDH – Pleural/Serum >0.6 >0.6
Pleural LDH
>2/3 upper limit of N serum LDH
>0.45 upper limit of N serum LDH
170
What is the usual presentation of exudative vs transudative pleural effusions
Transudative effusions are usually bilateral, not unilateral
Exudative effusions can be bilateral or unilateral
171
Transudative pleural effusion pathophysiology
• pathophysiology: alteration of systemic factors that affect the formation and absorption of pleural fluid (e.g. increased capillary hydrostatic pressure, decreased plasma oncotic pressure)
172
Transudative pleural effusion etiologies
■ CHF: usually right-sided or bilateral
■ cirrhosis leading to hepatic hydrothorax
■ nephrotic syndrome, protein losing enteropathy, cirrhosis
■ pulmonary embolism (may cause transudative but more often causes exudative effusion)
■ peritoneal dialysis, hypothyroidism, CF, urinothorax
173
Exudative pleural effusion pathophysiology
increased permeability of pleural capillaries or lymphatic dysfunction
174
Exudative pleural effusion etiologies
```
Infectious -
Parapneumonic effusion (associated with bacterial pneumonia, lung abscess)
Empyema (bacterial, fungal, TB)
TB pleuritis
Viral infection
Fungal
Parasitic
```
```
Malignancy -
Lung carcinoma (35%)
Lymphoma (10%)
Metastases: breast (25%), ovary, kidney
Mesothelioma
Myeloma
```
```
Inflammatory -
Collagen vascular diseases: RA, SLE
Pancreatitis
Benign asbestos related effusion
Pulmonary embolism
ARMS
Post-CABG or cardiac injury
Drug reaction
```
```
Intra-Abdomnal -
Subphrenic abscess
Pancreatic disease (elevated pleural fluid amylase)
Meigs’ syndrome (ascites and hydrothorax associated with an ovarian fibroma or other pelvic tumour)
```
```
IntraThoracic -
Esophageal perforation (elevated fluid amylase)
```
Trauma -
Hemothorax: rupture of a blood vessel, commonly by trauma or tumours
Pneumothorax (spontaneous, traumatic, tension)
Chylothorax
Iatrogenic
Other -
Drug-induced
Hypothyroidism
175
What does bloody pleural fluid suggest
Trauma
| Malignancy
176
What does white pleural fluid suggest
empyema
| chylous or chyliform effusion
177
What does black pleural fluid suggest
Aspergillosis
| Amoebic liver abscess
178
What does yellow-green pleural fluid suggest
Rheumatoid pleurisy
179
What does viscous pleural fluid suggest
Malignant mesothelioma
180
What does ammonia odour pleural fluid suggest
Urinothorax
181
What does food particles in pleural fluid suggest
Esophageal rupture
182
Signs and symptoms of pleural effusion
* often asymptomatic
* dyspnea: varies with size of effusion and underlying lung function
* orthopnea
* pleuritic chest pain
* inspection: trachea deviates away from effusion, ipsilateral decreased expansion
* percussion: decreased tactile fremitus, dullness
* auscultation: decreased breath sounds, bronchial breathing and egophony at above fluid level, pleural friction rub
183
What is the role of CT in evaluating pleural effusion
* To assess for fluid loculation, pleural thickening and nodules, parenchymal abnormalities and adenopathy
* Helps to distinguish benign from malignant effusion and transudative from exudative effusion
* May not distinguish empyema from parapneumonic effusion
184
Features of malignant pleural effusion
Multiple pleural nodules
185
Features of exudative pleural effusion
* Loculation
* Pleural thickening
* Pleural nodules
* Extrapleural fat of increased density
186
Pleural fluid investigations
• CXR
■ must have >200 mL of pleural fluid for visualization on PA film
■ lateral: >50 mL leads to blunting of posterior costophrenic angle
■ PA: blunting of lateral costophrenic angle
■ dense opacification of lung fields with concave meniscus
■ decubitus: fluid will layer out unless it is loculated
■ supine: fluid will appear as general haziness
* CT may be helpful in differentiating parenchymal from pleural abnormalities, may identify underlying lung pathology
* U/S: detects small effusions and can guide thoracentesis
• thoracentesis: indicated if pleural effusion is a new finding; be sure to send off blood work (LDH, glucose, protein) at the same time for comparison
■ risk of re-expansion pulmonary edema if >1.5 L of fluid is removed
■ inspect for colour, character, and odour of fluid
■ analyze fluid
• pleural biopsy: indicated if suspect TB, mesothelioma, or other malignancy (and if cytology negative)
187
Difference between simple and complicated effusion
Simple Effusion
pH >7.2
LDH <1/2 serum
glucose >2.2
```
Complicated Effusion
pH <7.2
LDH >1/2 serum
glucose <2.2
positive Gram stain Needs drainage
```
188
Why is protein and LDH measured in pleural effusion
Transudate vs. exudate
LDH especially high (>1000 IU/L) in empyema, rheumatoid, malignancy
Protein especially high in TB, myeloma
189
Why is Gram Stain, Ziehl-Nielsen Stain (TB), Culture done for pleural effusion
Looking for specific organisms
190
Why is cell count differential done for pleural effusion
Neutrophils vs. lymphocytes (lymphocytic effusion in TB, cancer lymphoma, serositis)
191
Why is cytology done for pleural effusion
Malignancy, infection
192
Why is glucose done for pleural effusion
Low (fluid:serum < 0.5) in rheumatoid, TB, empyema, malignancy, esophageal rupture
193
Why is rheumatoid factor, ANA and complement done for pleural effusion
Collagen vascular disease
194
Why is amylase done for pleural effusion
Pancreatitis, esophageal perforation, malignancy
195
Why is pH done for pleural effusion
```
Normally about 7.6
Very low (<7.0) in empyema, TB rheumatoid, malignancy, esophageal rupture
```
196
Why do we look for blood in pleural effusion
Mostly traumatic, malignancy PE with infarction, TB
197
When do you see triglycerides in pleural effusion
Chylothorax from thoracic duct leakage, mostly due to trauma, lung CA, or lymphoma
198
Why do we look for cholesterol in pleural effusion
Distinguish between chylous and chyliform effusion (seen in inflammation, e.g. TB RA)
199
Pleural effusion treatment
* thoracentesis treat underlying cause
| * consider indwelling pleural catheter or pleurodesis in refractory effusions
200
Complicated pleural effusion pathophysiology
* persistent bacteria in the pleural space but fluid is non-purulent
* neutrophils, pleural fluid acidosis (pH <7.00), and high LDH
* often no bacteria grown since rapidly cleared from pleural space
* fibrin layer leading to loculation of pleural fluid
201
Complicated pleural effusion treatment
• treatment: antibiotics depending on gram stain and chest tube drainage
202
Empyema definition
pus in pleural space or an effusion with organisms seen on a Gram stain or culture (e.g. pleural fluid is grossly purulent)
• positive culture is not required for diagnosis
203
Empyema etiology
• contiguous spread from lung infection (most commonly anaerobes) or infection through chest wall (e.g. trauma, surgery)
204
Empyema signs and symptoms
• fever, pleuritic chest pain
205
Empyema investigations
* CT chest
* thoracentesis
* PMNs (lymphocytes in TB) ± visible organisms on Gram stain
206
Empyema treatment
* antibiotic therapy for at least 4-6 wk (rarely effective alone)
* complete pleural drainage with chest tube
* if loculated, more difficult to drain – may require surgical drainage with video-assisted thorascopic surgery (VATS), or removal of fibrin coating (surgical or tPA/DNAse) to allow lung re-expansion (decortication)
207
Pneumothorax definition
presence of air in the pleural space
208
Pneumothorax pathophysiology
• entry of air into pleural space raises intrapleural pressure causing partial lung deflation
209
Pneumothorax etiology
* traumatic: penetrating or non-penetrating chest injuries
* iatrogenic (central venous catheter, thoracentesis, mechanical ventilation with barotrauma)
• spontaneous (no history of trauma)
■ primary (no underlying lung disease)
◆ spontaneous rupture of apical subpleural bleb (packets of air) of lung into pleural space
◆ smoker, male, family history, Marfan's syndrome
■ secondary (underlying lung disease)
◆ rupture of subpleural bleb which migrates along bronchioalveolar sheath to the mediastinum then to the intrapleural space
◆ necrosis of lung tissue adjacent to pleural surface
◆ pneumonia, abscess, PCP, lung CA, COPD, CF, TB
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When do you Need to Rule Out Life-Threatening Tension Pneumothorax and what is your first step
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If pneumothorax with:
• Severe respiratory distress
• Tracheal deviation to contralateral side
• Distended neck veins (Increased JVP)
• Hypotension
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Do not perform CXR Needs immediate treatment
211
Pneumothorax signs and symptoms
* can be asymptomatic
* acute-onset pleuritic chest pain, dyspnea
* tachypnea, tachycardia
* tracheal deviation (contralateral deviation in tension pneumothorax)
* ipsilateral diminished chest expansion
* decreased tactile/vocal fremitus
* hyperresonance
* ipsilateral diminished breath sounds
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Pneumothorax investigations
• CXR
■ small: separation of visceral and parietal pleura seen as fine crescentic line parallel to chest wall at apex
■ large: decreased density and decreased volume of lung on side of pneumothorax
213
Pneumothorax treatment
• primary spontaneous pneumothorax
■ stable, small (<3 cm), minimal symptoms: observation + O2
■ if symptomatic or large (>3 cm): aspiration
■ unstable/tension pneumothorax: needle decompression then chest tube, and VATS if unsuccessful (25-50%)
• secondary spontaneous pneumothorax
■ stable, small (<3 cm), minimal symptoms: observation + O2
■ if symptomatic, large, or unstable: chest tube, and VATS if unsuccessful
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Benign manifestations of asbestos exposure etiology and pathophysiology
■ “benign asbestos pleural effusion”
◆ exudative effusion, typically ~10 yr after exposure, resolves
■ pleural plaques, usually calcified
◆ marker of exposure; usually an asymptomatic radiologic finding
215
What is the etiology and pathophysiology of mesthelioma
■ primary malignancy of the pleura
■ decades after asbestos exposure (even with limited exposure)
■ smoking not a risk factor, but asbestos and smoking synergistically increase risk of lung cancer
216
Asbestos related disease signs and symptoms
persistent chest pain, dyspnea, cough, bloody pleural effusion, weight loss
217
Asbestos related disease investigations
* biopsy (pleuroscopic or open)
| * needle biopsy may seed needle tract with tumour
218
Asbestos related disease treatment
• resection (extrapleural pneumonectomy) requires careful patient selection; rarely successful (average survival <1 yr)
