Quiz 4 Flashcards
1
Q
Categorize COPD by airflow obstruction caused by
- anatomic narrowing of airway
- loss of elastic recoil
A
Anatomic narrowing of airway
- chronic bronchitis
- asthma
Loss of elastic recoil
-emphysema
2
Q
What is used to assess respiratory muscle strength?
A
Maximal respiratory pressures MIP and MEP
3
Q
What effect do asthma and chronic bronchitis have on diffusing capacity?
A
NONE!
4
Q
FRC in emphysema vs fibrosis compared to normal
A
Emphysema - higher FRC
-tendency of the lungs to collapse is less than the tendency of the chest wall to expand at normal FRC
Fibrosis - Lower FRC
-the tendency of the lungs to collapse is greater than the tendency of the chest wall to expand at normal FRC
5
Q
COPD vs asthma in terms of reversibility
A
COPD - NOT reversible
Asthma - reversible
6
Q
Fill in the blanks for definition of emphysema
(blank) enlargement of airspaces (blank) to terminal bronchioles accompanied by (blank x 3) w/out obvious fibrosis
A
- irreversible
- distal
- alveolar wall destruction
7
Q
Acinus is defined as
A
respiratory bronchiole and beyond
8
Q
Clinical definition for chronic bronchitis
A
Clinically defined as persistent cough with sputum production for at least 3 months/ year in at least 2
consecutive years without other identifiable cause
9
Q
List 4 morphological changes seen with chronic bronchitis
A
- Squamous metaplasia
- Goblet cell hyperplasia
- submucosal gland hyperplasia
- chronic inflammation
10
Q
Loss of what, seen with chronic bronchitis, leads to inc risk of infection?
A
CILIA
11
Q
List 2 organisms that cause recurrent infections in chronic bronchitis
A
- H. influenzae
- S. pneumoniae
12
Q
5 A’s for smoking cessation
A
Ask Advise Assess Assist Arrange
13
Q
What are side effects of Varenicline? What is it used for?
A
- Crazy dreams
- Shouldn’t be used in patients at increased risk of suicide
3 fold inc in smoking cessation
14
Q
Which class of emphysema is associated with spontaneous pneumothorax in young adults?
A
Paraseptal
15
Q
Lobe predominance for centriacinar vs panacinar emphysema
A
Centriacinar -> upper lobe
Panacinar -> lower zone
16
Q
pO2 level indicating hypoxemic respiratory failure? What should be given to the patient?
A
pO2 < 55 (<60 w/ evidence of RHF)
O2 therapy!
17
Q
List 4 radiographic manifestations of COPD
A
- Inc # of ribs -> hyperinflation
- Lung parenchyma attenuated in UPPER lung zones
- On lateral view - flat shape of diaphragm
- Should be dome shaped
- Retrosternal airspace due to hyperinflation
- Sign of air trapping
18
Q
Single most effective and cost-effective, intervention to reduce risk of developing COPD and its progression
A
SMOKING
19
Q
Which vaccine can reduce morbidity and death in COPD?
A
Influenza vaccine
20
Q
List 4 effects associated with use of systemic corticosteroids
A
- myopathy
- osteoporosis
- diabetes
- immunosuppression
21
Q
Long term administration of what has been shown to increase survival in COPD patients with resting hypoxemia? What should be checked before starting this tx?
A
- OXYGEN
- check pCO2 -> don’t want to suppress ventilation and make them even more hyercarbic
22
Q
COPD bronchodilator tx
A
- Inhaled tx preferred
1. SABA
- Anticholinergic
- tiotropium - LAMA (preferred)
- ipratropium - SAMA - LABA
- formoterol - Inhaled corticosteroid
- Budesonide
LABA + ICS may improve adherence
23
Q
COPD other pharmacological tx
A
- PDE inhibitors
- Theophylline
- Roflumilast (specific for PDE4) -> good for patients w/ bronchitic phenotype - Macrolides -> azithromycin, erythromycin
- anti-inflammatory; not antibiotics
- may inc antibiotics resistance
24
Q
Bronchiectasis
- what’s destroyed
- due to what?
- end result?
A
- muscular and elastic tissue of bronchi and bronchioles
- chronic necrotizing infection
- permanent dilation of airways
25
Why can hemoptysis occur with bronchiectasis?
extension of airway inflammation into adjacent artery
26
What is the defect in primary ciliary dyskinesia? what lung problem can it lead to?
- defect in dynein arm
| - bronchiectasis
27
Classic radiographic sign of bronchiectasis?
Signet ring sign
| -dilated bronchus compared to artery
28
When should surgical resection be considered for bronchiectasis?
ONLY for localized, non-progressive disease
29
Chronic inflammatory disorder characterized by airway hyperreactivity that leads to episodic bronchoconstriction (reversible bronchospasm) and hypersecretion of mucus
What is asthma?
30
What are 2 cytological findings of asthma?
1. Curschmann spirals - coiled basophilic plugs of mucus and detached epithelial cells
2. Charcot-Leyden crystals - eosinophil membrane protein
31
Most common chronic disease of childhood?
ASTHMA
32
Death rates in asthma are highest in which group?
Young adult african americans (15-24)
33
What are the 2 types of asthma
| -describe pathogenesis of each
1. ATOPIC (allergic/extrinsic)
- Type 1 IgE mediated HSR
- skin tests positive
- genetic predisposition -> allergic rhinitis + eczema
- environmental antigens -> dust, pollens, animal dander, foods
2. NONATOPIC (nonallergic/intrinsic)
- lacks allergen sensitization
- skin test negative
- family hx less common
- triggers -> viral infections, air pollutants, drugs (e.g. aspirin), chemical irritants
34
Describe the sensitization phase of atopic asthma. Discuss role of:
- T cells
- Interleukins
- Mast cell
- eosinophils
-allergens induce TH2 phenotype in CD4+ T cells of genetically susceptible individuals
- TH2 cells secrete IL-4, IL-5, IL-10
* IL-4, IL-5 -> class switching to IgE
* IL-5 -> calls in EOSINOPHILS
* IL-10 -> ability to inhibit production of Th1 helper T cells and induce production of Th2 T cells
-Mast cells bind IgE using at the Fc component -> sensitized to next allergen encounter
35
Early phase atopic asthma (minutes)
MEDIATORS
- leukotrienes
- prostaglandins
- acetylcholine
- histamine
- platelet activating factor
EFFECTS
- inc permeability of vessels -> edema
- smooth muscle constriction -> bronchoconstriction
- release of mucous
- loss of integrity of epithelium
36
Late phase atopic asthma (hours)
Inflammatory cells come in
Eosinophils -> release major basic protein which can aggregate to form charcot-leyden crystals
-promotes bronchoconstriction
37
viral induce inflammation may enhance (blank) mediated bronchoconstriction and edema
VAGAL
38
Describe aspirin intolerant asthma
- mechanism
- triad
Blocking COX will shunt arachidonic acid down LIPOXYGENASE pathway -> inc production of leukotrienes -> bronchospasms
Triad
- asthma
- bronchospasm
- nasal polyps
NOTE: this is NOT T1HSR
39
What bronchodilator response is expected with asthma?
inc of >12% AND 200ml in FEV1 or FVC
40
Bronchoprovocation testing
- standard
- positive test
- how long to wait after viral infection befor testing
- methacholine is standard
- histamine can also be used
PC20 < 20 mg/ml is positive
-concentration of methacholine required to lower FEV1 by 20%
-wait 8-12 weeks after viral infection to prevent false positive
41
Describe diurnal variation with asthma
Peak expiratory flow rate (PEFR) will show variability b/w AM and PM
>20% difference b/w AM and PM values of PEFR suggestive of asthma
42
Radiographic findings with asthma
- can be normal
| - hyperinflation w/ preservation of diaphragmatic dome
43
What is the best question to ask when assessing asthma control?
How well are you sleeping through the night?
44
b-2 receptor agonists
- best way to administer
- clinical use
- adverse effects
- CI
WARNING: LONG CARD!
Administration -> inhalant targeted deliver
CLINICAL USE
1. short-acting agents: mild, intermittent asthma, acute asthma
2. long-acting agents (& LACS): a component of treatment for
moderate to severe persistent asthma (& COPD)
ADVERSE EFFECTS
1. Black Box Warning: Increased asthma deaths occur with single
agent LABA usage
2. high dose effects: largely β2 atrial & β1 myocardial effects
- CV: HR and BP increases, tachycardia, arrhythmia
- CNS: nervousness, anxiety
- Skeletal muscle: tremors, fasciculations & weakness
- Metabolic effects:
a) INC liver & skel. muscle metab.;
b) INC plasma insulin, glucose & free fatty acids;
c) hypokalemia
CONTRAINDICATIONS
- Do not use non-selective β-blockers for Rx of hypertension in asthmatics;
- also cautious use of β2-agonists alone with diabetes, cardiac disease, hyperthyroidism or seizures
45
Tx for emergency asthma
1. I.V. epi (alpha, beta 1 and 2 agonist)
2. Terbutaline (beta-2 agonist)
3. O2
46
What are the proposed mechanisms for METHYLXANTHINES
How is metabolized?
Adverse effects?
MECHANISMS
1. Blocks phosphodiesterase
- inc cAMP levels due dec hydrolysis to AMP
- bronchodilation and dec inflammatory response
2. Blocks actions of adenosine
- dec histamine release
METABOLIZED -> cytochrome P-450
ADVERSE EFFECTS
- narrow TI index due to
- cardiotoxicity
- neurotoxicity
47
Theophylline
- class
- clinical use
- side effects
- cautions
- metabolized
- contraindications
1. Class -> methylxanthine
2. Clinical use - oral-slow release
A) for severe and nocturnal asthma and bronchospasms
-2nd or 3rd line for asthma
B) COPD and bronchitis
-for resp fatigue
-may improve sensitivity to corticosteroid tx
3. Side effects
A) CNS (PDE4) -> headaches, nervousness, anxiety
B) Cardiac (PDE3) -> PVCs, Palpitations, arrythmias
C) GI irritation (AD1-R) -> vomiting, abdominal-upset, pain, diuresis
High levels -> seizures, arrhythmias,d death
4. Cautions
- MUST MONITOR BLOOD LEVELS
5. Metabolized -> Cyt P450
6. CI -> pregnancy
48
Ipratropium
Tiotropium
- Class
- MoA
- Indications
- Drug of choice for?
1. Class -> muscarinic/cholinergic receptor antagonist
- Ipratropium - SAMA (6-8 hour)
- Tiotropium - LAMA ( >12 hr)
2. MoA
- antagonists at M1 and M3 receptors
- dec IP3, DAG and Ca -> bronchodilation and dec secretion of mucous
3. Indications
A) refractory chronic asthma -> add tiotropium (LAMA) to LABA and ICS
-esp. non allergic airways hyper-reactivity
-SAMA not so good for chronic asthma tx but can be used in acute severe exacerbations
B) Drug of choice for COPD -> IMPORTANT
49
Name 2 corticosteroids used for chronic asthma
beclomethasone, fluticasone
50
Cromolyn sodium
- MoA
- uses
- cautions and concerns
1. MoA
- stabilizes mast cell -> dec histamine release
- inhibition of mast cell and sensory nerve Cl- channels
```
2. Uses
A) PROPHYLACTIC
-before exposure to allergens/exercise
B) COPD and Asthma
C) Used in combination w/ b2 agonist for PEDIATRIC ASTHMA CONTROL
```
3. Cautions
- FEW; very well tolerated and extremely safe
51
List 2 leukotriene receptor inhibitors
Montelukast and zafirlukast
-first aid says -> specially good for ASA induced asthma
52
MoA of Zileuton
Inhibits 5-lipoxygenase
-blocks conversion of arachidonic acid to leukotriene
-good for ASA induced asthma
53
Common adverse effect amongst the 3 leukotriene pathway/receptor inhibitors
LIVER TOXICITY -> zileuton in particular
54
Omalizumab
- MoA
- use
- cautions
- how long does it take to work?
1. MoA
- monoclonal anti-IgE Ab
- binds to unbound serum IgE -> blocks binding to FceRI
2. Use
- severe asthma resistant to inhaled steroids and LABA
- positive allergen test
3. Cautions
- CRS -> anaphylactic shock
- rare
4. Duration for action
> 3-4 months needed
-weak response
55
SABA for asthma
- name 2 drugs
- when should they be used/not be used?
- a parameter to measure?
– Examples: albuterol, levalbuterol
– Therapy of choice for acute relief of symptoms
– Should be available to all asthmatics (unless intolerant)
– Use only as needed for acute relief. Scheduled use not advantageous and may be deleterious to some pts.
– Frequency of use is parameter to assess/guide therapy
56
LABA for asthma
- name 2 drugs
- recommended for?
- how should it be used?
- black box?
– Examples: formoterol, salmeterol
– Preferred adjunctive therapy to add to ICS (Steps 3-6)
– NEVER use as monotherapy in asthma (contrasts with
COPD)
– Not currently recommended for treatment of acute
symptoms or exacerbations
– “Black Box” warning in package insert but benefits likely to outweigh risks for vast majority of pts.
57
What is the preferred drug for the following in asthma tx and why?
1. Monotx of mild persistent disease
2. Control med for persistent disease regardless of severity or control
INHALED CORTICOSTEROIDS -> Most potent and effective anti-inflammatory med for asthma
58
If you had a choice b/w leukotriene modifiers and LABA when adding an adjunct to ICS, which one should you use?
LABA
59
In which cases leukotriene modifiers be considered? (list 3)
- asthmatics w/ rhinitis
- exercise induced bronchospasm
- aspirin sensitivity
60
What can be used as monotx or adjuct when oral tx is indicated for asthma?
Methylxanthines (theophylline)
61
Systemic corticosteroids for asthma
- when to use?
- how to administer?
- risk of what if course > 10 -14 days
1. Use
- acute exacerbation
- chronic tx only for the worst cases
2. Method
- burst or taper (typically 4-10 days)
3. Adrenal suppression
62
Parameters to assess asthma impairment
* Frequency of sx’s
* Nocturnal awakenings
* Frequency of SABA use
* Interference with activity
* Lung function (spirometry)
* Questionnaire scores
* Treatment-related adverse effects
63
Parameters to assess asthma risk
* Frequency of exacerbations requiring systemic steroids
* Severity of exacerbations (hospitalization, intubation)
* Potential for long-term lung impairment or adverse tx effects
64
What's the end stage of Interstitial lung diseases?
HONEYCOMB LUNG - effacement of normal archictecture
65
What's the difference b/w ARDS and acute interstitial pneumonia?
AIP is idiopathic
66
Describe the color changes seen with Raynaud's phenomenon
Raynaud's syndrome associated with which 3 conditions?
White -> blue -> red
- conn tissue disease
- SLE
- CREST syndrome
67
List one drug from the following medication classes that is associated with pulmonary fibrosis
- chemo agents
- antiarrhythmics
- antibiotics
- another cancer treatment (not drug)
- chemo agents -> bleomycin
- antiarrhythmics -> amiodarone
- antibiotics -> nitrofurantoin
- another cancer treatment (not drug) -> radiation
FROM FIRST AID
"Breathing Air Badly from Medications"
Bleomycin
Amiodarone
Busulfan
Methotrexate
68
Occupational exposures:
1. Silicosis
2. Asbestosis
3. Talcosis
4. Hard Metal Disease (which metals)
1. Silicosis
- hard rock mining
- foundry work
- sandblasting
- glass/pottery making (porcelain flour)
2. Asbestosis
- Shipyards
- boilers/HVAC
- plumbing
- construction trades
3. Talcosis
- latex
- plastics
4. Hard metal disease (cobalt, tungsten, beryllium)
- metal foundry
- tool/die maker
- Beryllium -> used in aircraft parts
69
Beryllium mimics?
SARCOIDOSIS
70
Compare the crackles of usual intersitial pneumonia to heart failure
UIP -> inspiratory crackles
-sounds like velcro (crisp)
Heart failure -> expiratory crackles
71
Compare A-a gradient during exercise in usual intersitital pneumonia vs normal
Normal
-TV inc and A-a gradient stays the same or even decreases
UIP
- inc in rate rather than TV w/ exercise
- Inc dead space to TV ratio
- progressive hypoxemia
- WIDENED A-a gradient
72
Gold stand for ILD dx?
SURGICAL LUNG BX
73
Bronchoscopic parenchymal bx is limited to?
Granulomatous diseases
| -due to size and sampling artifact
74
Interstitial inflammation in usual interstitial pneumonia consists of which cell types?
- lymphocytes
- plasma cells
- macrophages
75
Name 3 systemic autoimmune diseases associated with the same pattern as idiopathic interstitial pneumonia. What is this pattern? Why is it important to understand this?
Pattern -> chronic interstitial pneumonia with fibrosis
Autoimmune diseases
1. Progressive systemic sclerosis
2. Rheumatoid arthritis
3. SLE
Important because we can treat the autoimmune diseases!
76
What is thought to be the major driver in the progression of Idiopathic pulmonary fibrosis?
TGF-BETA
- released from injured pneumocytes as part of healing process (cyclic lung injury is involved with IPF)
- but can promote fibrosis and predispose to more injury
77
Interstitial fibrosis in IPF is most pronounced where?
Periphery and lower lung zones
78
List 2 radiographic and 2 gross findings associated w/ IPF
Radiographic
- reticular opacities
- focal ground glass opacities
Gross
- honeycombing
- traction bronchiectasis -> fibrosis causes traction and pulls on the airways
79
Describe the clinical presentation of IPF
```
• Insidiously progressive dyspnea
• Dry, hacking cough
• Less commonly
– Fatigue
– Weight loss
– Myalgias/arthralgias
```
80
Currently used tx for IPF?
| Potential future tx (ASCEND trial)
Current
- O2
- lung transplant
Future
-Pirfenidone -> reduces effects of TGF-beta
81
Hypersensitivity pneumonitis
- which type of hypersensitivity?
- which lymphocytes are increased?
- how does the lymphocytes type compare with sarcoidosis?
Type III (immune complex) and Type IV (cell mediated)
-CD8+ T cells
Sarcoidosis -> CD4+ T cell response to unknown antigen
82
What is the relationship between smoking and hypersensitivity?
Smoking seems to protective from hypersensitivity pneumonitis
83
CXR finding with hypersensitivity pneumonitis
1. Reticulonodular infiltrates
- UPPER zone predominant (note that IPF is lower lobe)
- sparing of costophrenic angles
2. Occasional alveolar opacification
3. honeycombing (end stage)
84
Histological findings of hypersensitivity pneumonitis
1. expansion of interstitium with chronic inflammatory cells
2. ill-defined granuloma
- no necrosis
-patchy process w/ bronchiocentric pattern
85
Tx for hypersensitivity pneumonitis
1. REMOVE AND AVOID THE ANTIGEN
2. Corticosteroids
- prednisone -> 1mg/kg/d w/ gradual taper over 3-6 months
86
Sarcoidosis patient population
1. adults < 40
- peaks at 25-34
2. Women > men
3. AA > whites
87
Describe the heterogeneity in disease presentation of sarcoidosis
Japan
Europeans
Puerto Ricans
1. Japan -> inc ocular and cardiac involvement
2. Europeans -> erythema nodosum
3. Puerto Ricans -> lupus pernio
88
List sarcoidosis organ involvement for most common to least common
lung > skin = ocular > neurological = CV > MSK
89
Lofgren's syndrome triad
acute sarcoidosis
1. Erythema nodosum
2. bilateral hilar adenopathy
3. fever
90
CV abnormalties seen with sarcoidsosis
1. Electrical
- dysrhythmias -> sudden death
- heart block
2. Infiltrative cardiomyopathy
3. pericardial effusion -> can turn into tamponade
91
Sarcoidosis ocular invovlement
| -which one is an emergency?
Uveitis -> EMERGENCY
- painful, red eye
- give steroids
Lacrimal glands -> dry eye
-can mimic sjogren's
Conjunctiva
-granuloma formation
92
Why do sarcoid patients tend to have hypercalciuria and hypercalcemia
Non-caseating granulomas makes 1-alpha-hydroxylase -> inc vit D3 -> inc Ca and PO4 absorption from gut -> stones
93
What pattern do sarcoid granulomas follow?
Lymphangitic
- interlobular septate along veins
- subpleural area
- along bronchovascular bundles
94
Staging for sarcoidosis pulmonary involvement
0 - normal
I - bilateral hilar lymphadenopathy
II - bilateral hilar lymphadenopathy + interstitial infiltrates (start here)
III - interstitial infiltrates; no bilateral hilar lymphadenopathy
IV - pulmonary fibrosis
95
Tx for sacoidosis
1. Coricosteroids
- systemic
2. Cytotoxic agents
- MTX
- azathioprine
- cyclophosphamide
3. antimalarials (hydroxychloroquinine)
- cutaneous involvement
- hypercalcemia
4. Biological modifiers
- infliximab
96
Sarcoidosis prognosis
- remission
- chronic progressive course
- cause of death
1. remission = 2/3
2. chronic progressive course = 10-30%
3. cause of death
- respiratory involvement
- cardiac
- neurological
97
Blood supply to the pleura
| -visceral vs parietal
Visceral -> bronchial arteries
-low pressure
Parietal -> costal arteries
-high pressure
98
Familial pneumothorax is associated with mutation in?
Folliculin gene (birt-hogg-dube syndrome)
99
Pneumothorax physical findings
- breath sounds
- percussion
- fremitus
dec breath sounds
hyperresonant to percussion
dec tactile fremitus
100
Where should the thoracostomy tube be placed relative to ribs?
ABOVE the rib b/c neurovascular bundle is below
101
Pleural effusion vs consolidation
- breath sounds
- percussion
- fremitus
Pleural effusion
- dec breath sounds
- dullness to percussion
- dec fremitus
Consolidation
- later inspiratory crackles
- dullness to percussion
- INC fremitus
102
What are 2 causes of pleural effusion?
| -give an example of each
1. Inc pleural fluid formation
- increases interstitial fluid in the lung
2. Dec pleural fluid absorption
- obstruction of lymphatics draining the parietal pleura
103
Transudate vs exudate
what the only 3 things that can cause an exudate?
Light's criteria for exudate?
Transudate
- low protein
- due to CHF, nephrotic syndrome or hepatic cirrhosis
Exudate
- high protein
- cloudy
- malignancy, pneumonia, collagen vascular disease, trauma etc.
Light's criteria - need only 1/3 to classify exudate
1. pleural fluid to serum protein ratio > 0.5
2. pleural fluid to serum LDH ratio > 0.6
3. pleural fluid LDH > 0.6 upper limit of normal
104
Glucose of < 60 in pleural fluid can indicate? (2 things)
1. Complex parapneumonic process/empyema (infection)
| 2. Rheumatoid pleurisy
105
Complication associated with pleural effusion and pneumothorax?
Re-expansion pulmonary edema -> rapid re-expansion of collapsed lung
106
Which type of pleural effusion a person with a kidney stone at risk for getting?
Urinothorax
- pleural fluid Cr to serum Cr > 1
- due to obstructive uropathy
- this is uncommon
107
Triglyceride > 110 mg/dL in pleural fluid indicates?
Chylothorax
108
describe the path for the thoracic duct from inferior to superior
cisterna chyli -> through diaphragm posterior to aorta (T12) -> crosses from right to left b/w T4 and T10 -> drains into left subclavian vein
109
List the paraneoplastic syndromes associated with the following lung cancers
1. Small cell
2. Squamous cell
1. Small cell
- ACTH
- ADH (SIADH)
2. Squamous cell
- PTHrp -> hypercalcemia
110
Asbestos + smoking -> inc risk for???
primary lung cancer (50-90x RR)
111
Histoplasmosis vs cancer on CXR
look similar but CALCIFICATION more common with histo
112
Mets vs primary neoplasm of lung - what's more common?
METS
113
Immunostaining for squamous cell vs adenocarcinoma
1. Squamous cell
p63+, TFF1-
2. Adenocarcinoma
TTF-1+, p63-
Goljan trick - just remember one
114
Adenocarcinoma is defined by the presence of???
- peripheral or central
- most common lung tumor in?
GLANDS OR MUCIN
- peripheral
- most common tumor in non-smokers and female smokers (pathoma)
115
Most common tumor in male smokers?
- peripheral or central
- characteristics?
Squamous cell carcinoma
- central
- keratin pearls
- intracellular bridges
116
If no characteristics of squamous, adeno, or small cell carcinoma what's the cancer?
-list 2 characteristics
large cell carcinoma
- abundant cytoplasm
- prominent nucleoli
117
Staging and treatment for lung cancer
- 0-II
- III
- IV
0-II -> surgery
III -> chemo/rad and maybe surgery
IV -> chemo/rad
118
What stage if you have mets or malignant effusion?
IV
119
Small cell lung tx
how does this differ from tx for NSCLC?
CHEMO/RADIATION - Mets even if can't see it
NSCLC - tx based on stage and patient status
-could be surgery, chemo/rad or both
120
Carcinoma vs sarcoma incidence in kids vs adults
Incidence of carcinomas (epithelium) < sarcomas (hematological) in kids
OPPOSITE FOR ADULTS
121
Standard of care drug in patients with adenocarcinoma?
| -what does this drug target?
Gefitinib -> targets EGFR which is a commonly mutated in adenocarcinoma
122
SPHERE of complications see with lung cancer:
| -first aid
```
Superior vena cava syndrome
Pancoast tumor
Horner syndrome
Endocrine (paraneoplastic)
Recurrent laryngeal sxs (hoarseness)
Effusions (pleural or pericardial)
```
123
What's a unique site that lung cancer likes to metastasize to?
ADRENAL GLAND
124
List 1 pro and 1 con of doing lung cancer screening
Pros
-low dose CT in high risk patients can dec mortality by 20%
Cons
- 96% false positive rate (many are non-calcified nodules)
- 7% of these have invasive procedure
125
Solitary pulmonary nodule that:
- peripheral
- well circumscribed
- mature tissues in lung (which ones?)
THINK?
Hamartoma
- fat
- cartilage
most common BENIGN tumor in the lung
126
List 2 epithelioid carcinoma that can involve the pleura
Malignant mesothelioma
Adenocarcinoma
Need to do immunohistochemical staining to differentiate
127
Most common marker seen on IH chem for malignant mesothelioma?
Calretinin
128
How to tell a sarcomatoid malignant mesothelioma from a sarcoma?
MM -> cytokeratin positive
129
Serum marker under study for mesothelioma?
Plasma fibulin 3 levels
130
Cystic fibrosis
- inheritance
- incidence
- gene
- chromosome
- inheritance -> autosomal recessive
- incidence -> 1:3000 births in U.S.
- gene -> CF gene codes for cystic fibrosis transmembrane conductance regulator (CFTR)
- chromosome -> 7
131
Infective organism vs age in CF patients
Peds -> staph
Pseudomonas aeruginosa -> later age
-peaks around 25-34
132
What type of pseudomonas infection do we want to avoid in CF patients as long as possible?
Mucoid PsA
| -forms biofilm -> chronic infection -> rapid drop in FEV1
133
What is the mainstay antibiotic used to manage chronic PsA infection? How about early infection?
Chronic -> Tobramycin cycles (TOBI trial)
-inhaled antibiotic
Early -> tobramycin for 28 days -> 90% chance of getting rid of infection (EPIC trial)
134
Management of acute pulmonary exacerbation
- age difference
- why is it important to avoid APEx?
Young -> oral antibiotics
older -> IV
APEx associated with decline in BASELINE lung fx
135
Which infection do all CF patients worry about (hint: onions)
-why do they worry?
Burkholderia cepacia
Cepacia syndrome -> life expectancy drops by 9 years
-can lead to death within weeks
136
What's used to manage inflammation in CF?
which outcomes are improved with use of this drug?
Azithromycin - changes inflammatory response of white cells
Improved outcomes
- better FEV1
- greater percentage of pulm exacerbation free days
137
Azithromycin use and outcome in patients with PsA infection?
Patients without PsA infection?
1. PsA +
Improved outcomes
-better FEV1
-greater percentage of pulm exacerbation free days
2. PsA neg
- no change in lung fx (b/c it was already good to begin with)
- weight improvement
- less cough
138
CF patients tend to have deficiencies in which vitamins?
```
fat soluble (ADEK)
-think about why each of these are important
```
vit D - bone disease
vit K - bleeding problems
139
What is the most common CFTR class? what's the problem?
Class II -> folding problem + domain assembly -> protein is degraded
DeltaF-508
-deletion in phenylalanine at position 508
85% of patients have this mutation
Problem with N and Po
140
3 factors that influence CFTR anion transport
N x Po x G = total Cl- transport
N - number of channels at plasma membrane
Po - time each channel spends open vs closed
G - size of each Cl channel
Modulators will target these areas to in CF tx treatment
141
What one drug approved for CF tx? Where does it act?
Ivacaftor (VX-770)
- targets GATING mutations in CFTR (e.g. G551D)
- improves Po
- approved for ALL gating mutations
142
Phase III trial that improved protein to 30% of normal in patients with F508del combined which 2 modulators
VX-770 (ivacaftor) + VX-809 (F508 correction)
VX-770 -> improves Po
VX-809 -> improves N
143
Dornase alpha mech
mucolytic
RhDNase -> cleaves DNA and makes the mucous less sticky
144
What's used to improve hydration in CF patients?
7% saline (hypertonic)
145
Histoplasmosis capsulatum
- geography
- mimics
- ohio and mississippi river valley
| - mimics Tb
146
Which component of histo is infectious?
Microconidia
147
List 3 dimorphic fungi that cause systemic disease in humans.
-why are they dimorphic?
1. Histoplasmosis capsulatum
2. Blastomyces dermatidis
3. Coccidiodes immitis
148
Blastomyces dermatitidis
- region
- gender pref
- upper or lower lung field
- key area of dissemination
- appearance of bud
-endemic eastern US, reported from Africa
first aid: east of mississippi and central america
- males>females
- lower lung field
- skin
- broad based bud (same size as RBC)
149
Coccidioidomycosis
- region
- conditions
- associated with which fever
- dissemination difference by race
- how does it infect
- mould culture
- life cycle
- southwest U.S., Mexico, central and south america
- arid, alkaline soil
- san joaquin valley fever
- dissemination higher in non-caucasian (may be HLA related)
- arthroconidia -> easily aerosolized -> highly infectious
- Mould in culture at room temp AND 37 -> IMPORTANT
- can grow in routine culture (3-10 days)
-inhaled arthroconidia -> spherules -> endospores -> spherules
NOTE:
-spherules -> induce granulomatous response
-endospores -> attract neutrophils
150
Cryptococcus neoformans vs gattii
- location and assoc
- pulmonary disease
- morphology
- how is it acquired
C. neoformans
- temperate climates
- assoc -> bird droppings (pigeons)
C. gattii
- tropical and subtropical climates
- assoc -> eucalyptus trees
- vancouver island/pacific NW outbreak
- pulmonary disease less likely to be subclinical
BOTH
- encapsulated yeast
- not dimorphic -> IMPORTANT
- acquired through inhalation
151
MCC of mycotic meningitis
Cryptococcus
152
Dx for cryptococcus
Antigen test for presence of polysaccharide shed from capsule (glucuronoxylomannan)
-HIGH SENSITIVITY AND SPECIFICITY in CSF/serum
153
5 A's of aspergillus fumigatus
- is it dimorphic
- dx?
A’s for Aspergillus:
- Acute Angle < 45 degrees
- Allergic Aspergillosis/Asthma -> IgE and eosinophils
- Aspergilloma -> infection in preformed lung cavity "fungus ball"
- Angioinvasive -> hits all the organs
- Aflatoxin -> hepatocellular carcinoma
- Amphotericin B
NOT dimorphic
Dx - antigen test for galactomannan
154
HIV and Tb reactivation association
+10% annual risk
155
Primary vs reactivation Tb lung zone
Primary
-ghon focus in MID zone of lung
Reactivation
- apex of lung
- no ghon focus
156
When is risk of reactivation Tb the highest?
w/in 2 years after primary infection
157
First line drugs for Tb (RIPES for tx)
R - rifampin -> inhibits DNA-dependent RNA polymerase
I - isoniazid (INH) -> dec synthesis of mycolic acid
P - pyrazinimide
E - ethambutol
S - streptomycin (cidal agent)
INH and rifampin kill intra and extracellular bacilli
158
Out of the bacterial causes of pneumonia discussed in saelinger lecture, which 2 have vaccines?
Strep pneumo
- gm pos cocci
- community acquired pneumo (CAP)
Haemophilus influenza
- gm neg coccobacillus
- CAP in COPD, alcoholics and elderly
159
Most common cause of community acquired pneumonia?
| List 2 major virulence factors for this organism
Streptococcus pneumoniae
virulence factors
- capsule
- pneumolysin -> cytotoxic
160
Haemophilus influenzae
- morphology
- serotype which most commonly causes human infections
- virulence factor
- vaccine (>6 months vs less)
Morphology
-gm neg coccobacilli; fastidious
Serotype
-Hib
Virulence factor
-capsule
Vaccine
- T-independent antigen -> if > 6 months
- T-dependent antigen -> if < 6 months; capsular carb conjugated to protein
161
Mycoplasma pneumoniae
- characteristics
- age group and spread
- major virulence factor
- presentation
- vaccine
- tx
1. Characteristics
- NO cell wall
- pleomorphic
- cold agglutinins - IgM
- requires media w/ STEROLS; fastidious
- fried egg appearance
- has BOTH RNA and DNA
2. Age and spread
- 5-19 years
- spread through droplets and requires close prolonged contact
3. Virulence
- extracellular
- adheres to respiratory epithelium
- no alveolar involvement
- P1 attachment factor!!
4. Presentation
- tracheobronchitis - MC
- atypical pneumonia
- walking pneumonia -> mild sxs and lasts weeks
5. No vaccine
6. Tx
- macrolides -> block 50S ribosome
- fluoroquinolones -> inhibit DNA gyrase and topoisomerase IV
162
Legionella pneumophila
- characteristics
- major virulence factor
- presentation (be specific)
- vaccine
- what's needed to resolve disease process
- treatment
- dx
1. Characteristics
- hard to stain; silver stain+
- fastidious in lab
- growth in ameba
- no human to human contact
- aerosolized water droplets
- CAP and hospital acquired
2. Major virulence factors
- facultative intracellular -> macrophages
- virulence factors enhance phagocytosis + intracellular survival and growth
3. Presentation -> legionnaire's
- cough: scant sputum
- high fever (104+)
- GI sxs
- primary manifestation = pneumonia
- Mortality 16-20%
4. No vaccine
5. cell mediated immunity is needed to resolve disease process
6. Tx
- macrolides
- fluoroquinolones
7. Dx
culturing on BCYE (slow) + urinary antigen test (rapid; only for serotype 1)
163
What is the most common infectious serotype of Legionella pneumophila? why is this important?
SEROTYPE 1 - only serotype for which a rapid lab test is available
-urinary antigen test
164
Pontiac fever
Non-pneumonic legionella infection
- flu like illness
- may be a HSR
165
Chlamydiaceae
| -extracellular or intracellular
OBLIGATE INTRACELLULAR BACTERIA
166
Chlamydophila psittaci vs C. pneumoniae with regards to:
- natural host
- disease in humans
- frequency
Chlamydophila psittaci
- host = birds and non-human animals
- disease = pneumonia
- frequency = rare
C. pneumoniae
- host = humans
- disease = acute respiratory disease
- frequency = COMMON
167
Klebsiella pneumoniae
- characteristic
- which patient population
- give away keywords
1. characteristics
- gm neg rod
- enterobacteriaceae
2. Patients likely to aspirate
- alcoholics
- long term care facilities
- opportunistic infection
3. MUCOID capsular material
- "currant jelly"
168
Pseudomonas aeruginosa
| -characteristics
- Gm neg rod
- oxidase positive (cytochrome oxidase)
- non-fermenter
169
Chronic vs acute pseudomonas infection and predisposing factors
Chronic
- Cystic fibrosis (mucoid strain)
- mucoid exopolysaccharide (MEP) -> biofilm production (BAD NEWS!!!)
Acute pneumonia
- Ventilation acquired pneumonia (VAP)
- comatose, sedated patients on vent
170
Which virulence factor is shared by pseudomonas and diphtheria?
Exotoxin A = diphtheria toxin -> ADP ribosyltransferase -> inactivates ef2 -> stop protein synthesis
171
Which isolates of pseudomonas have the following characteristics:
- mucoid
- quorum sensing
- loss of flagella, pili, o side chains and downregulation of production of toxins
Cystic Fibrosis ISOLATES
172
All RNA viruses replicate in the (blank) except for (2 blanks)
Cytoplasm except influenza and retroviruses
173
Amantadine and rimantadine block
viral uncoating and genome release
| -influenza A only
174
Neuraminidase inhibitors prevent
sialic acid removal -> no spread of virus
- influenza A and B
- zanamivir and oseltamivir
175
what causes a pandemic - drift or shift?
Shift -> novel virus due to reassortment of viral genes
176
Systemic sxs from influenza infection are caused by?
Endogenous interferon release (not due to the virus itself)
177
Influenza virus is more stable in (cold/warm) air and (low/high) humidity
COLD air and LOW humidity
178
Influenza A virus
- characteristics
- virulence
- disease systems involved
- vaccine
1. Characteristics
- neg sense, single stranded RNA virus with envelope
- 8 segmented genome
- replicates in nucleus
2. Virulence
- HA -> viral entry
- NA -> release
3. upper and lower respiratory tracts
4. YES
179
Respiratory syncytial virus (RSV) is a disease of which season?
WINTER
180
MCC of lower respiratory disease in infants?
RSV - major resp pathogen of young children
-bronchiolitis and bronchopneumonia
181
RSV (paramyxovirus)
- characteristics
- virulence
- disease systems involved
- vaccine
- tx
1. Characteristics
- neg sense, single stranded RNA virus with envelope
- NON-segmented
- replicates in cytoplasm
2. Virulence
- Fusion (F) protein -> syncytia formation
- attachment proteins
3. resp tract, bronchioles
4. NO
5. Tx -> ribavirin
182
Parainfluenza (paramyxo)
- characteristics
- virulence
- disease systems involved
- vaccine
1. Characteristics
- neg sense, single stranded RNA virus with envelope
- NON-segmented
- replicates in cytoplasm
- several serotypes
2. Virulence
- Fusion (F) protein
- attachment proteins
3. upper and lower resp tract; CROUP
4. NO
183
Croup also called? what's the unique presentation?
Laryngotracheobronchitis
seal like cough
also stridor
184
Describe mech of pertussis toxin
ADP-ribosylation
disables Gi -> over activates adenylate cyclase (inc cAMP)
Leads to
- immunosuppression
- inhibition of chemotaxis
185
3 stages of pertussis cough
- which one is most contagious
- which one has the worse cough
1. Catarrhal
- MOST CONTAGIOUS
- lasts 1-3 weeks
2. Paroxysmal
- WORST COUGH (paroxysmal cough)
- lasts 2-6 weeks
3. Convalescent
- lasts 2-3 weeks
186
Bordetella pertussis
- characteristics
- virulence
- disease systems involved
- vaccine
1. Characteristics
- gm neg rod
- fastidious growth (potato agar)
2. Virulence
- many
- pertussis toxin = ADP ribosyltransferase
3. Disease
- whooping cough
4. Vaccine -> YES!!!
- against adhesins
- vaccine doesn't last lifetime -> need booster
187
Should antibiotics be given for aspiration pneumonitis?
not usually -> clears up into 24 hours
188
Why is azithromycin added to ceftriaxone for hospitalized patients w/ CAP?
Azithro covers:
- legionella
- chlamydia
- mycoplasma
189
Good antibiotic for aspiration pneumonia?
-how about in the hospital?
Clindamycin -> good activity against anaerobes
Hospital aspiration
- vanc + carbapenem
- piperacillin/tazobactam
190
Tx for chlamydia or mycoplasma
doxycycline -> inhibits 30S
Azithromycin or clarithromycin
191
Tx for legionella
- Azithromycin
- quinolone
- can combine if severe
192
What antibiotics are good for pseudomonas?
- cefepime -> 4th gen cephalosporin
- carbapenem ->
- piperacillin/tazobactam
193
necrotizing bronchiolitis seen with bacterial or viral lung infections?
VIRAL
194
Acute vs chronic rhinosinusitis
Acute < 4 weeks
Chronic > 12 weeks
195
Viral URI vs acute bacterial rhinosinusitis
| -compare duration
viral lasts 5-10 days
bacterial > 10 days
196
Radiography for sinusitis
- usually don't need to image for acute
| - do CT for chronic after giving tx
197
most common organisms for acute bacterial rhinosinusitis in ADULTS
Strep pneumo
H. influenza
198
most common organisms for acute bacterial rhinosinusitis in KIDS
M. cat
strep pneumo
H. influenza
199
What organisms to consider with chronic bacterial rhinosinusitis
staph
pseudomonas -> especially w/ prior sinus surgery
Anaerobes
+ all the ones that cause acute
200
Steroid for sinusitis
- spray
- systemic
Sprays - only good chronic, NOT acute
systemic (prednisone) - excellent for acute AND chronic
201
Epworth sleepiness scale greater than what should warrant a sleep study for OSA?
10
202
AHI or RDI classification for mild, moderate and severe OSA
mild: 5-15
moderate: 15-30
severe: >30
203
most effect tx for OSA?
CPAP - improvement in
- daytime sleepiness
- quality of life
- cognitive fx
- systolic and diastolic BP
204
Patients with OSA due to what can have fantastic outcome through surgery
enlarged tonsils and/or adenoids
205
Mallampati classification is used to assess ease of (blank) but also correlates with severity of (blank). A score of IV means?
intubation; sleep apnea
Class IV - only hard palate is visible (worst)
206
Friedman classification used to predict success of?
Uvulopalatopharyngoplasty (UPPP)
| Class I -> successful
207
Rhinovirus
| -characterstics
small, naked, ssRNA
MCC common cold
208
Coronavirus
- characteristics
- common cold percentage
- which other disease
- enveloped
- single stranded RNA, + sense
- replicates in upper resp and GI tracts
15-30% of common colds
SARS
209
MC bacterial cause of pharyngitis?
- reservoir
- transmission
- M protein
- pyrogenic exotoxin (SPEA, B, C) responsible for?
- vaccine?
Strep pyogenes
Gm positive beta hemolytic streptococci
-in chains
- reservoir -> throat (infected humans only)
- transmission -> person to person
- M protein -> antiphagocytic; many serotypes
- pyrogenic exotoxin (SPEA, B, C) responsible for RASH of scarlet fever
- vaccine -> NO; too many M protein serotypes
210
Corynebacterium diphtheriae
- characteristics
- lab culture
- virulence
- disease
- vaccine
ABCDEFG (first aid)
1. Characteristics
- gm pos rod
- pleomorphic
- club shaped
2. Lab culture
- black colonies on cystine-tellurite agar
3. Virulence
- diphtheria toxin (A/B) -> ADP-ribosylation of elongation factor 2 -> stops protein translation (what else does this?)
4. Disease
- pseudomembranous pharyngitis
- lymphadenopathy
- myocarditis
- arrhythmias
5. Vaccine -> YES
- DPT
```
ADP-ribosylation
Beta-prophage
Corynebacterium
Diphtheriae
Elongation Factor 2
Granules
```
211
EBV
- characteristics
- virulence
- disease (list 4 aspects of this disease)
- vaccine
- primary infection asymptomatic in?
1. Characteristics
- enveloped, DNA
- herpesvirus
2. Virulence
- latency in B cells
3. Disease -> infectious mono
- fever, pharyngitis, lymphadenopathy (posterior cervical), and splenomegaly
4. No vaccine
5. primary infection often asymptomatic in children
212
The atypical lymphocytes seen in infectious mono are?
Reactive cytotoxic T cells (first aid)
213
Mumps virus
- characteristics
- virulence
- disease (list 4 aspects of this disease)
- vaccine
Mnemonic -> POM
1. Characteristics
- enveloped RNA paramyxovirus
- humans = sole reservoir
2. Virulence
- enter resp tract
- SYSTEMIC spread
3. Disease
- mumps -> parotitis, SYSTEMIC infection
4. Vaccine
YES -> MMR
Mumps make your parotid glands as big as POM-poms
P - parotitis
O - orchitis
M - aseptic Meningitis
214
Mumps is contagious before or after parotitis develops?
BEFORE!!!
215
H1-R effect on bronchial smooth muscle
CONTRACTION
GPCR -> DAG -> IP3 -> inc Ca++ -> contraction of smooth muscle
216
H2-R effect on gastric parietal cell
Inc in H+, pepsin secretion
GPCR -> inc in adenyl cyclase -> cAMP -> PKA -> H+,K+ - ATPase
217
Combined H1/H2-R dependent tissue response
- on vasculature
- skin -> triple response
H2 -> smooth muscle dilation
H1 -> endothelial cell contraction; edema
-NO release -> vasodilation
Skin -> triple response
- flush, flare, and wheal
- inc edema, pain and dilation
218
Dif b/w 1st and 2nd gen anithistamines
1st gen -> sedating
-lipophilic -> crosses BBB
2nd gen -> longer half life
219
2nd gen H1R antagonists metabolized by the?
P450 enzymes - drug drug ix
220
What should be used instead of antihistamines in the following situations when there's an emergency
- anaphylaxis
- shock
- acute asthma
- COPD
EPINEPHRINE
221
Which population should use antihistamines with caution?
Pregnant women
Heart disease
222
H2-R antagonists are generally very safe drugs
- where do they act?
- what's the exception drug?
Act on gastric parietal cells -> reduce H+ and pepsin production
- lower cAMP
- inhibit vagal and gastric stimulation of H+ production
Cimetidine - garbage drug
- inhibits P450
- inhibits hormone binding to androgen receptors and estradiol metab -> gynecomastia and impotence in men + galactorrhea in women
223
SPIKES for delivering bad news
SETUP
i. Have a plan before going into room
ii. Sit down
iii. Make eye contact
iv. Get close to patient
v. Have tissues
PERCEPTION (of the patient)
i. What does the patient know?
ii. Expectations of the patient
iii. Misconceptions or misunderstanding
iv. Is patient in denial
INVITATION
i. How much info does patient want?
KNOWLEDGE
i. Speak at level of patient
ii. Don’t use medial jargon
iii. Be direct
iv. Align patient perception
EMPATHIZE
i. Let them cry
ii. Ask is they have questions or concerns
SUMMARIZE
i. Be concrete about next steps
ii. Make sure they understand
