First Pass Miss Flashcards
What pressures are equal at FRC?
Elastic recoil of the chest wall (intrapleural - atmospheric) = elastic recoil of lungs (alveolar - intrapleural)
remember, recoil = inside - outside
Elastic recoil of lungs = transpulmonary pressure
What is La Place’s relationship and how is related to surfactant?
P =2T/r
If surface tensions were equal in small vs large alveoli, greater filling pressures would be required to inflate the smaller alveoli.
Surfactant helps reduce T more the small your alveoli, keeping filling pressures equal no matter alveolar size.
What is meant by effort dependence vs effort independence?
For the first 25% of the expiratory flow curve, increasing the intrapleural pressure more will increase flow more. However, at a certain point, an increase in intrapleural pressure will not generate a greater expiratory flow. This is called “effort independent” expiratory flow.
What is the rate constant of an alveolus?
The time it takes to empty or fill an alveolus.
RC
R = resistance, C = compliance. Increasing resistance or increasing compliance will increase the filling / emptying time.
Stiffer lungs with lower resistance will empty faster
What is the resistance formula for the lungs?
R = P/V
Where P = pressure difference and V = airflow
Think of this is a rearrangement of V=IR, where current = airflow, and voltage = pressure difference
What is the nitrogen washout curve / what explains closing volume?
Put a patient on one breath of 100% O2, the slowly exhale while expired volume and nitrogen concentration are measured.
Phase 1 - 100% O2 from dead space
Phase 2 - Rapid increase in nitrogen as lung units start emptying
Phase 3 - plateau
Phase 4 - when near RV, the apex of the lungs which carried high N2 air from the anatomical deadspace begin contributing. From where this nitrogen upslope begins to the end of expiration (RV) is called closing volume.
What is the definition of vital capacity in terms of lung volumes?
VC = TLC - RV
TLC = total lung capacity
What is the clinical utility of diffusing capacity for carbon monoxide?
If spirometry shows a restrictive process:
- > Low DLCO suggests parenchymal disease
- > normal DLCO suggests chest wall disease
What does an elevated RV with a low TLC suggest?
Neuromuscular disease
- > cannot fully inspire to TLC
- > Cannot use accessory muscles to fully exhale
What are the causes of increased TLC?
- Obstructive lung diseases
2. Acromegaly - increased size of lung parenchyma
How is the oxygen content of blood calculated?
CaO2 = (1.39 * Hgb * SaO2) + 0.003 * PaO2
Where PaO2 is the arterial oxygen tension, used to calculate dissolved arterial O2 (makes a much smaller contribution than hemoglobin)
Hgb is hemoglobin concentration
How can the partial pressure of O2 gas in an alveolus be predicted?
Alveolar gas equation
PAO2 = PiO2 - PaCO2 / R
PiO2 = inspired O2 partial pressure PaCO2 = arterial partial pressure of CO2 R = respiratory quotient
What is the normal A-a gradient and how does it change as you age?
About 10mmHg
Gradient increases about 2.5 mmHg per decade.
Equation:
PaO2 = 100 mmHg - (age in years/3)
I.e. if PAO2 = 100 mmHg, then 2 decades after age 20 (age 40), PaO2 = 85 mmHg expected.
60 years:
PaO2 = 100 - (60/3) = 80 mmHg
What is the PaO2 which qualifies patients for home oxygen?
55mmHg -> corresponds to 88% on SaO2. Below this level, there is a rapid decrease in SaO2 with decreasing PaO2 (highly sloped portion of the curve)
What is the chloride shift / what causes it?
CO2 enters RBC. HCO3- starts to accumulate due to carbonic anhydrase. Membrane is impermeable to H+, and so it is buffered by hemoglobin to HHb. As HCO3- begins to build in the cell, HCO3- is antiported with Cl-, dropping Cl- in venous blood (chloride shift)
Three carrying forms of CO2 included: carbamino proteins, dissolved CO2, and bicarbonate anion
How do you calculate anion gap and what is the normal range?
AG = [Na+] - ([Cl-] + [HCO3-])
Normal = 10-12 mEq/L
What is anion gap useful for?
Differential diagnosis of metabolic acidosis
- > increased = unmeasured anions in the blood
- > normal = loss of base caused acidosis
- > hypoalbuminemia causes DECREASED anion gap metabolic acidosis
- > causes retention of chloride and bicarbonate
What are the causes of respiratory alkalosis and what is the only chronic one?
Hypoxemia of any cause (will cause hyperventilation)
Anxiety, pain, fever
Airway disorders: asthma and COPD can go both ways, pulmonary edema and pneumonia as well
Salicylates (increases breathing frequency to cause respiratory alkalosis along with metabolic acidosis)
Pregnancy: mild, chronic hyperventilation
What are the causes of metabolic acidosis WITHOUT anion gap?
Base loss:
HCO3- loss from diarrhea
Diuretics: acetazolamide -> causes loss of HCO3-
Pure acid: HCl
Renal tubular acidoses and early renal failure
Give acute causes of respiratory acidosis?
Asthma / COPD - both can go both ways depending on level of obstruction
Drug overdose (opioid)
Stroke
Neuromuscular diseases like Guillain-Barre
Give chronic causes of respiratory acidosis?
Obesity-hypoventilation syndrome (restrictive)
COPD
Kyphoscoliosis
Neuromuscular: ALS, myasthenia gravis
How do you tell pulmonary artery vs bronchial artery vs pulmonary veins?
Pulmonary artery - about the same size as the bronchioles they travel with (adjacent to)
Bronchial artery - also travels adjacent to, but is much smaller than bronchioles and pulmonary arteries
Pulmonary veins - empty alveolar capillaries, run in the interlobular septae and subpleural connective tissue rather than near airways
What populates the mucosa of the trachea and how is it different than a bronchus?
- Tall, pseudostratified columnar epithelium with goblet cells
- Lamina propria connective tissue with blood vessels (to warm the air)
Difference from bronchus - no muscularis mucosae, since the cartilage is so strong
How do bronchi differ from trachea?
- Bronchi has muscularis mucosae in the mucosal layer
- The cartilage is made of plates rather than continuous.
- Epithelium transitions from pseudostratified to simple ciliated columnar
How do bronchioles differ from bronchi?
- No cartilage
- No submucosal glands
- Thick muscularis mucosa relative to airway lumen
- Simple ciliated columnar becomes simple cuboidal with club (Clara) cells
What the features of hairy leukoplakia and why? Who does it happen in and how does it appear under the microscope?
White plaque with folds and tiny hair-like protrusions usually on lateral surface of the tongue which CANNOT be scraped off
Thickening of the mucosa due to proliferation in squamous epithelial cells, keratin is very white.
Happens in HIV patients who are smokers and have EBV infection
Will cause hyperkeratosis, or parakeratosis if the nuclei are still present
Balloon cells -> present in stratum spinosum, cells appear inflated and pale
What typically causes the development of pyogenic granuloma and how is it treated?
Typically related to irritation or hormonal (often during pregnancy)
Treated with excision (curative), but often regresses in pregnant women, or can even progress to ossify if untreated
-> it is excessive granulation tissue forming a polyploid mass on buccal mucosa
What are the risk factors for squamous cell carcinoma in the lower lip and the oropharynx?
Overall for all: alcohol, tobacco, chewing betel nut
Lower lip - UV radiation, pipe smoking
Oropharynx - HPV, especially HPV16
What syndrome is associated with development of melanosis inside the mouth and hamartomatous polyps of the GI tract?
Syndrome is associated with gingival hyperplasia?
Peutz-Jeghers syndrome;
Acute Monocytic Leukemia
A patient comes in with a locally aggressive and destructive benign neoplasm of the nasopharynx causing epistaxis. Name and describe his condition, and what demographics he most likely is?
Nasopharyngeal angiofibroma (it is aggressive despite being benign)
Highly vascular neoplasm which causes profuse bleeding and has a high recurrence rate
Almost exclusively in adolescent males, especially with fair skin and red hair
What does nasopharyngeal carcinoma look like microscopically? Who is it found in? Who has the best prognosis?
Appears like poorly differentiated squamous cell carcinoma (pleomorphic, keratin-positive), surrounded by lymphocytes (mostly T cells to fight EBV infection)
Found in African children and Chinese adults with EBV infection, and especially smokers and those exposed to nitrosamines
Nonkeratinizing carcinomas fare much better than keratinizing, as tumor must be susceptible to radiation therapy
How do laryngeal squamous papillomas present different in adults vs children, and what do they look like?
Present as single in adults, but multiple in children
Look alot like genital warts but on vocal cords -> covered with stratified squamous epithelium. High recurrence rate.
-> caused by HPV 6 and 11
How does squamous cell carcinoma of the larynx differ from oral cavity in terms of course, and how does it present?
Larynx has a more linear progression from dysplasia -> carcinoma in situ
Oral cavity is more random
Presents with hoarseness, in middle-aged male smokers
Can also be caused by HPV, but HPV 6/11 rather than HPV 16 (oropharyngeal)
What is paraseptal emphysema and what causes it? Where in the lung is it most severe?
It is “distal acinar” emphysema -> destruction of most distal alveolar ducts and alveoli, adjacent to areas of pulmonary fibrosis
Typically occurs in upper lobes, especially subpleural areas of upper lobes.
Cause is unknown
-> often presents with spontaneous pneumothorax
What is it called when air dissects into connective tissue within lungs, and then moves thru mediastinum and subcutaneous tissue, even reaching face? What causes this?
Interstitial emphysema
Caused by trauma (i.e. tension pneumothorax) or increased intraalveolar pressure (i.e. due to ventilator)
What is the definition of chronic bronchitis? What is it characterized by?
Presence of a persistent, productive cough without discernable cause for >3 months each year for at least 2 years in a row
Due to smoking, characterized by hyperplasia of submucosal glands, hyperplasia of muscularis mucosa, mixed inflammatory infiltrates, and epithelial squamous metaplasia and dysplasia
What are the clinical features of chronic bronchitis?
- Chronic cough with sputum production (diagnostic)
- Eventual dyspnea and cyanosis / right heart failure
- > blue bloaters - Recurrent pulmonary infections
What airway remodelling occurs in asthma in the bronchi / bronchioles?
From top to bottom:
- Globlet cell metaplasia / mucous gland hyperplasia
- Sub-basement membrane fibrosis
- Edema of submucosa with inflammatory cell infiltrate with eosinophils, increased vascularity
- Smooth muscle hyperplasia / hypertrophy (chronic bronchoconstriction)
-> sub-basement membrane fibrosis and eosinophils are best way to tell apart from chronic bronchitis
What diagnostic things of asthma are contained in the mucous plugs?
Curschmann spirals - mucoid swirls of epithelial cells
Charcot-Leyden crystals - needle-like structures formed by extruded and coalesced granules of eosinophils, next to eosinophils
What causes bronchiectasis and what will happen distally?
Decreased ciliary function (i.e. kartagener’s or cystic fibrosis) or chronic bronchitis leads to recurrent infections, which cause distal resportive atelectasis, continual loss of structural support, and permanent dilatation of airways with decreased clearance of secretions
-> extends to pleura, especially in lower lobes, due to gravity
What causes patchy atelectasis? Contraction atelectasis?
Loss of pulmonary surfactant -> respiratory distress syndromes
Contraction atelectasis is associated with fibrosis
Describe the pathogenesis of compression atelectasis. What are some of the causes? How does the mediastinum shift?
Pulmonary compression collapses the lung
Causes: Accumulation in the pleural cavity (pleural effusion, hemothorax, pneumothorax), diaphragmatic elevation (peritonitis, abscess, or critically ill post-op patients) -> leads to basal atelectasis
Mediastinum shifts AWAY from overfilled area -> emergent situation
Give three reasons why there is increased work of breathing in asthma.
- Increased airway resistance due to bronchoconstriction
- Hyperinflation of lung flattens diaphragm, which cannot optimally stretch prior to contraction -> more work
- Hyperinflated lungs sit higher on lung compliance curve, where lung is less compliant
(higher FRC and RV in acute attacks)
What is the pattern of decline in lung function in asthma and how is this prevented?
Biphasic decline in FEV1
Early - within 2 hours, a small decline due to initial release of histamine and production of leukotrienes (blocked by antihistamines / leukotriene antagonists)
Late - Peaking in 6-8 hours, remaining inflammatory cells lead to bronchial hyperreactivity -> prevented by leukotriene antagonists and corticosteroids
What is the dichotomy which is most important to make when diagnosing asthma, and how is this done?
Intermittent vs Persistent (mild, moderate, or severe)
Intermittent asthma defined by rule of 2’s
Symptoms <= 2 days a week
Awakenings <= 2x a month
Use of SABAs <= 2 days a week
<2 a year having exacerbations requiring systemic corticosteroids
No interference in normal activity
Give two biologics which are used to control asthma and their role in therapy?
Omalizumab -> binds IgE
Mepolizumab -> anti IL-5
Role: poorly controlled asthmatics, who require high-dose inhaled corticosteroids and have frequent hospitalizations
What three things can tip you off that a COPD exacerbation is occurring and what usually causes it?
- Change in sputum quality
- Increase in shortness of breath
- New or increased cough
Usually due to a bacterial or viral infection
What are the systemic changes which occur in COPD?
- Weight loss -> due to increased work of breathing and circulating TNF -> cachexia (being fat increases survival)
- Skeletal muscle dysfunction
- Osteoporosis
- Cardiovascular morbidity / mortality
What are the four GOLD category cutoffs?
GOLD 1: FEV > 80% predicted
GOLD 2: 50 < FEV < 80
GOLD 3: 30 < FEV < 50
GOLD 4: FEV < 30% predicted
What are the primary inflammatory cell types found in COPD? How does this relate to its overall severity compared to asthma?
Macrophages, T lymphocytes (CD8+), and neutrophils
These cell types are less responsive to steroids -> ICS not as good for preventing exacerbations of COPD
(mast cells in asthma respond to ICS well)
How is dyspnea managed in COPD?
Long-acting beta agonists or Long-acting anticholinergics are drugs of choice, despite no significant benefits to lung function via spirometry.
Ipratropium or albuterol can be used for rapid relief
Theophylline!! is seeing a comeback in patients with severe disease
Steroids only used in exacerbations systemically, or inhaled in incredibly severe COPD
Use O2 if PaO2 < 55 mmHg
What are the periods of lung development up until age 20? What develops in each of these stages?
Lung bud = 4-6 weeks - up to segmental bronchi
Pseudoglandular period = 6-16 weeks - up to terminal bronchioles
Canalicular period = 16-26 weeks - up to alveolar ducts
Saccular / Alveolar period = 26 weeks to term - up to terminal sacs
Alveolar period = birth to 10 years - up to adult alveoli number
10-20 years - HYPERTROPHY of existing alveoli
What agents accelerate lung maturation?
Think asthma drugs / stimulants
Steroids - i.e. betamethasone Stress Thyroxine Theophylline Sympathomimetics Prolactin (increases late in pregnancy)
What are two extra lobes of the lung which occur not uncommonly?
Azygous lobe -> right upper lung at apex
Cardiac lobe -> right lower lung
Generally asymptomatic
What is the difference between a bronchogenic sequestration and cyst?
Sequestration - clinically very similar to cysts, except there is no connection to tracheobronchial tree.
Importantly:
Cyst - supplied by low pressure PULMONARY circulation
Sequestration - supplied by high pressure SYSTEMIC circulation - more difficult to remove
What factors make RDS more or less likely?
More likely - diabetic mothers (insulin), prematurity (prior to 30 weeks), C-section birth (less stressful for baby than uterine)
Less likely - intrauterine stress, heroin-addicted mothers
What are the complications of RDS / its treatment and how do you prevent the eye manifestation?
RIB due to O2
Retinopathy of prematurity - prevent with vitamin E
Intraventricular hemorrhage - germinal matrix
Bronchopulmonary dysplasia -> alveolar hypoplasia
Necrotizing enterocolitis - with pockets of air called pneumatosis intestinalis
What causes the three types of immotile cilia syndromes?
Type 1 - Kartagener’s - dynein arms absent
Type 2 - defect of radial spokes
Type 3 - Transposition of A and B microtubules (A normally has dynein arms)
What is the common pathogenesis of dust-related lung disease?
Chronic inhalation of particles -> phagocytosis by alveolar macs with eventual oversaturation -> longstanding activation of macrophages with induction of the inflammosome
- > production of IL-1 and IL-18
- > release of ROS, eicosanoids, cytokines, and fibroblast growth factors (i.e. TGF-beta)
-> cellular injury and pulmonary fibrosis
What happens overtime to lung function as a result of silicosis and what are the additional complications are associated?
Slowly worsening pulmonary function and pulmonary hypertension
- Inhibition of macrophages -> increased susceptibility to mycobacterial infections (both TB and non TB) -> especially upper lobes
- Increased risk of autoimmune disorders from chronic macrophage overactivity
What two types of cells are microscopically identified in mesothelioma?
- Atypical epithelioid - plump, rounded to columnar
2. Sarcomatoid - spindle-shaped
How is berylliosis pathogenesis unique versus the other pneuomoconioses?
Genetic predisposition plays a large role -> due to a Type IV, delayed-type hypersensitivity
-> beryllium + protein is presented on MHC Class II of APCs, activating CD4+ Th1 cells and ultimately macrophages
