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
What characterizes the overall pathology of berylliosis (chronic beryllium disease)?
Formation of non-necrotizing granulomas, followed by fibrosis
- > occurs most frequently in lung, impairing pulmonary function
- > beryllium is also absorbed through skin, so granulomas can appear systemically, looks like sarcoidosis
What is the pulmonary pathology of Caplan syndrome?
Multiple well-defined round, peripheral lung nodules (rheumatoid nodules) comprised of mineral dust and degenerating collagen which is completely surrounded by fibrobalsts and macrophages
- > nodules can cavitate or calcify
- > if your nodules (i.e. in silicosis) are very large but you have this, your prognosis is much better than if you’re not RF+
What is hypersensitivity pneumonitis and how does it differ from asthma?
Extrinsic allergic alveolitis
- > this is hypersensitivity of the small airways and alveoli (similar to chronic bronchitis or emphysema)
- > asthma affects the large airways
What is the pathogenesis of the acute phase of hypersensitivity pneumonitis? Give symptoms.
Flu-like symptoms within hours of antigen exposure. Resolves in hours to days
Type III hypersensitivity -Immune complex formation and tissue deposition, with complement activation and Ig deposition in vessel walls
What is the pathogenesis of subacute or chronic phase of hypersensitivity pneumonitis? Give symptoms.
Insidious, progress dyspnea, cough, and fatigue
Type IV hypersensitivity
- > delayed-type = CD4 cell activation and macrophage coactivation, creating poorly-formed granulomas
- > cytotoxic = sensitization of certain antigen-specific CD8 T cells -> apoptosis of target cells
What is the second most common cause of bacterial exacerbation of COPD? What is it morphology?
1 cause: Nontypable H. influenzae
Moraxella catarrhalis
-> gram negative diplococci
What is the difference between gray and red hepatization?
Red hepatization (firm like liver) -> happens earlier, with numerous erythrocytes, neutrophils, and fibrinous exudate
Gray -> more macrophages now as well, and RBCs have become lysed and eatin by neutrophils / MACs
preceded by congestion (hyperemia), followed by resolution
What are the patient symptoms of lung abscess?
Fever, productive cough with foul-smelling and bloody sputum (trying to clear airway), weight loss (TNF from inflammation)
->** digital clubbing, due to growth factors released from abscess reaching systemic circulation
How does atypical pneumonia appear pathologically?
Interstitial pneumonia - cells stay in the interstitium because lymphocytes (needed to fight viruses) cannot extravasate like neutrophils
- > mononuclear infiltrate within septae
- > occasionally complicated by alveolar damage and hyaline membrane formation
What are the clinical symptoms / signs of atypical pneumonia?
Low grade fever
Dry cough (nothing in airspaces to cough up)
Mild leukocytosis (primarily lymphocytes)
Often preceded by URI
vs typical:
Acute onset of fever, tachypnea, productive cough, elevated WBCs, pleuritic chest pain / cough
Who is Nocardia asteroides complex most frequently associated with? Where does it disseminate to?
Those with depressed cell-mediated immunity (prolonged steroid use most common, also HIV, transplant)
- > disseminates to CNS (think of the bullet going through the hat of the cowboy as he coughs)
- > disseminates to skin (think of his cow print clothes with red inflammation around them)
What are the diagnostic tests best used for diagnosis of histoplasmosis and blastomycosis?
Histoplasmosis - urine and serological testing (think of red and yellow stalactites in sketchy)
Blastomycosis - Culture is definitive, organism grows fast
Coccidioides do skin testing or serological testing
What is required for positive diagnosis of TB via sputum sampling?
At least three sputum samples taken 8 hours apart, with at least one being a morning sample
Three positives required, negative does not exclude TB
-> use these for culture in broth, 4-14 days
What is the rule used to interpret a positive PPD test?
5/10/15 mm rules
5 or more: positive if HIV, CXR consistent with TB, any immunosuppression, or recent TB contacts
10mm or more: recent travel from high prevalence area, IV drug use, lab personnel, age <5 (common in young children), BCG vaccine falls here
15mm or more: positive even with no other known factors
What are common and more specific symptoms of primary coccidioidomycosis?
Highest risk groups and where does it spread?
Fever, cough, joint aches (guy kneeling in sketchy)
Erythema nodosum - think shin lesions on wall in sketchy
Young or old, immunosuppressed, blacks, mexicans, and native americans
Can disseminate to skin (erythema nodosum) or cause fatal meningitis (think of guy leaning on immunocompromised fountain with neck brace)
How can hepatotoxicity caused by INH be told apart from rifampin?
Rifampin - causes increases in bilirubin and alkaline phosphatase
Isoniazid - causes aminotransferase elevations
What is the threshold value for LFT elevation with GI upset, and what should you do if the patient is below this to make them feel better? What should be avoided?
<3x the upper limit of normal
For symptomatic relief: Antacids, or take drugs with a light snack (crackers). Avoid too much food or there may be poor absorption -> especially antacids with FQs as the cations may limit absorption.
If the rash is petechial in nature, what drug does this make you think is causing the drug reaction?
Rifampin or its derivatives
-> hallmark of rifamycin hypersensitivity is associated thrombocytopenia
What patients are at greatest risk for toxicity from isoniazid?
Slow acetylators - metabolism occurs in liver initially by N-acetyltranferase
What is the common pathology of UIP?
Subpleural and bibasilar accentuation of tissue damage (extensive fibrosis)
->heterogeneity of tissue damage with “fibroblastic foci” - extensive fibroblast proliferation with ECM
What is seen in the pathology of DIP?
Large numbers of alveolar macrophages in the alveoli
Interstitium is filled with lymphocytes, fibrosis is only mild and rarely progresses to honeycomb
-> associated with smoking and excellent prognosis upon cessation
What is NSIP and what are its two subtypes? Which has worse prognosis?
Nonspecific Interstitial Pneumonia -
Second most common interstitial lung disease, it is an IP that does not fit into any of the other histological categories
Subtypes:
Cellular - (closer to DIP)
Fibrotic - Worse prognosis (closer to UIP)
-> NSIP also has an even distribution of fibrosis (vs UIP)
What levels are found to be elevated in diagnosis of sarcoidosis with bronchoalveolar lavage? What lab tests will be elevated?
Elevated CD4+:CD8+ T cell ratio (more CD4 cells due to activation of granulomas)
Noncaseating granulomas of sarcoidosis also elevated blood calcium (increased vitamin D levels due to 1-alpha-hydroxylase activity of macrophages) and elevated ACE (made in granuloma)
How are Langerhans cell histiocytoses identified histochemically?
CD1a surface antigen - identifies Langerhans cells
Along with endosomal Birbeck granules and folds in nuclear membrane
What is the development of Eosinophilic Granuloma / PLCH associated with? Who tends to get it?
Usually young adults
Strong association with smoking
-> relieved by cessation of smoking
-usually make a stellate appearance in the upper lobes
What is the most common subtype of lung cancer? What lung cancers have the highest incidence in smokers vs nonsmokers?
Adenocarcinoma is most common
Nonsmokers - primarily adenocarcinoma
Smokers - primarily squamous cell carcinoma, second highest is small cell carcinoma
Which tumors are most likely to present with pleural effusion / chest pain and distant metastases and why?
Pleural effusion / chest pain - Adenocarcinoma, Large cell carcinoma
-> grow more peripherally
Distant metastases - Adenocarinoma, Large cell carcinoma
-> more distal so they present later
Also small cell carcinoma -> since its so aggressive
What is the only type of lung cancer which currently has targetable molecular alterations? What molecular target is this and who is it seen in?
Adenocarcinoma
Seen in non-smokers and female smokers
Molecular target is EGFR mutations (not seen in other cancers) - EGFR inhibitors
What is the current view of the progression of adenocarcinoma?
- Normal terminal bronchioles / alveoli - Club cells and Type II pneumocytes
- Atypical adenomatous hyperplasia (AAH)
- > large Type 2 pneumocytes / interstitial space with hyperchromasia - Adenocarcinoma in situ (AIS)
- structure preserved - Invasive adenocarcinoma
- desmoplasia and destruction of normal airspaces
What additional mutation is most common in small cell carcinoma which accounts for its invasiveness?
Rb deletions (rapid progression through cell cycle by failure to block E2F-dependent production of cyclin E)
What are the signs and symptoms of interstitial lung diseases?
Dyspnea, especially with exertion (progresses over years, look at past imaging)
Dry cough
Hypoxemia
Clubbing of digits -> from growth factors released in fibrosis
Extra signs / symptoms related to specific diseases
What interstitial lung diseases follow an acute pattern?
Acute interstitial pneumonitis (AIP) -> looks like ARDS
Interstitial lung diseases manifesting with alveolar hemorrhaging
- >
- Churg Strauss (allergic granulomatous angiitis)
- >
- Microscopic polyangiitis (leukocytoclastic vasculitis)
- >
- granulomatous pulmonary angiitis (GPA)
1&2 here we’ve studied before and are associated with p-ANCA
What are the major risk factors for IPF (idiopathic pulmonary fibrosis, also called UIP)?
Tobacco smoking and acid reflux (GERD refluxes into airways), inhalation of wood dusty, EGFR TKI use
Can also be familial
What is the treatment for IPF and what is definitiely not effective? Prognosis?
Treatment - anti-fibrosis agents such as Nintedanib and Pirfenidone
Prognosis - poor, median survival 3 years, may progress to AIP
What are the possible nervous system and heart manifestations of sarcoidosis?
Ocular - anterior and posterior uveitis
Skin - lupus pernio (skin lesions looking like lupus butterfly rash), erythema nodosum (usually on shins, like due to endemic mycoses)
Nervous system: **Bell’s palsy, neuropathy, hypothalamic and pituitary lesions which can lead to SIADH or diabetes insipidus
Heart involvement: Sudden death due to complete heart block
->reminds me of Lyme disease
What are the common imaging findings of sarcoidosis? How are PFTs affected?
calcified hilar lymph nodes, and peribronchial distribution favoring the upper lobes (lymphangitic pattern, though pattern of restriction may mimic asthma)
-> PFTs may be normal or have restrictive pattern
What is the main treatment for sarcoidosis and when do we treat?
Steroids, or methotrexate if not responsive (immunomodulator)
Treat in two scenarios:
- Active / progressive lung disease
- Extrapulmonary symptoms
biopsy is needed to confirm diagnosis
What will PFTs and imaging show with cryptogenic organizing pneumonia (COP)?
PFTs - usually restrictive pattern
Imaging - bilateral and peripheral (bronchiolar) asymmetric patchy infiltrates, with or without air bronchograms
->alveoli often show ground glass appearance and reversed halo sign (ground glass with opacity on outside)
What are the neuroendocrine tumors and their generally shared morphology? What is the neuroendocrine marker?
Small Cell Carcinoma, and Typical / Atypical Carcinoid tumors
Grow in nests and plates, surrounded by richly vascularized stroma
Neuroendocrine marker - chromogranin
What are the molding and crush artifacts which are so characteristic of small cell carcinoma?
Molding - cells are growing so fast that they leave their expression on the adjacent cell and appear to mold together
Crush artifact - Threads of crushed DNA will be dispersed across the histological slide
There will also be spotty necrosis due to overgrowth
What are the histological features of typical carcinoid tumor?
Low grade
- > low N/C ratio
- > prominent granular cytoplasm
- > “salt and pepper” fine chromatin distribution with absent or few nucleoli
- > NO necrosis (vs SCC)
- > low proliferative rate
- > still arranged in nets juxtaposed to rich capillary network
What defines something as an Atypical carcinoid tumor?
Has a typical carcinoid morphology, but has EITHER 1. increased mitotic rate or 2. necrosis (typically occurs in punctate, bean-shaped foci)
What will PFTs and imaging show with cryptogenic organizing pneumonia (COP)?
PFTs - usually restrictive pattern
Imaging - bilateral and peripheral (bronchiolar) asymmetric patchy infiltrates, with or without air bronchograms
->alveoli often show ground glass appearance and reversed halo sign (ground glass with opacity on outside)
What accounts for cytoplasmic vacuolization in adenocarcinoma and how is it definitively told apart from SqCC?
cytoplasmic vacuolization - exocrine differentiation with accumulation of intracellular secretory vesicles (i.e. mucin)
Told apart via immunohistochemistry (SqCC will have keratin)
What are the neuroendocrine tumors and their generally shared morphology? What is the neuroendocrine marker?
Small Cell Carcinoma, and Typical / Atypical Carcinoid tumors
Grow in nests and plates, surrounded by richly vascularized stroma
Neuroendocrine marker - chromogranin
What are the molding and crush artifacts which are so characteristic of small cell carcinoma?
Molding - cells are growing so fast that they leave their expression on the adjacent cell and appear to mold together
Crush artifact - Threads of crushed DNA will be dispersed across the histological slide
There will also be spotty necrosis due to overgrowth
What are the histological features of typical carcinoid tumor?
Low grade
- > low N/C ratio
- > prominent granular cytoplasm
- > “salt and pepper” fine chromatin distribution with absent or few nucleoli
- > NO necrosis (vs SCC)
- > low proliferative rate
- > still arranged in nets juxtaposed to rich capillary network
What defines something as an Atypical carcinoid tumor?
Has a typical carcinoid morphology, but has EITHER 1. increased mitotic rate or 2. necrosis (typically occurs in punctate, bean-shaped foci)
What lung cancers are known for causing hypercalcemia and how do they do it?
Squamous cell carcinoma > Adenocarcinoma > small cell carcinoma
Caused by secreted of parathyroid hormone-related protein (PTHrP), or straight calcitriol
What endocrine paraneoplastic syndromes are most commonly associated with small cell carcinoma and how do these manifest clinically?
Syndrome of Inappropriate Antidiuretic Hormone (SIADH) -> causes hyponatremia
Excessive secretion of ACTH causing Cushing’s syndrome
-> moon facies, fluid retention, buffalo hump
Lambert-Eaton myasthenic syndrome - antibodies to presynaptic Ca+2 ACh channels
-> will get better thruout the day, and also cause autonomic symptoms
Formation of auto-antibodies to neurons
-> paraneoplastic myelitis, cerebellar ataxia, etc
What lung cancer is especially associated with hypertrophic osteoarthropathy? What is it?
Adenocarcinoma
New bone formation on distal long bones causing arthritis, as well as clubbing of fingers
What is the recommendation if you have an SPN (solitary pulmonary nodule, up to 3 cm), and what clinical factors are tied to highest risk of malignancy?
Non-contrast CT scan of chest. If low-risk, follow by CT for 2 years. If high risk, excise it
Increased risk -> advanced patient age and significant smoking
What are the clinical signs of pleural effusion?
Dullness to percussion, absence of fremitus, diminished / absent breath sounds, friction rub
Also signs & symptoms of underlying etiology of pleural effusion
What processes cause an exudate in the pleural effusions?
Pleural inflammation, infection, or malignancy -> high protein pulmonary edema (i.e. pneumonia, PE, malignancy)
Leaking from surrounding tissue -> mediastinum if esophagus ruptures, or chylothorax
Abdominal infections
want to do ultrasound to prevent forming pleural adhesions
What additional tests should be ordered on the pleural fluid if there is clinical suspicion of the following causes:
- Pancreatitis
- Chylothorax
- Cholethorax
Pancreatitis - amylase
Chylothorax - triglycerides:
>110 mg/dL is diagnostic (should appear milky white)
Cholethorax - bilirubin
What are the criteria for cholesterol and protein absolutely to cause pleural effusion an exudate without serum to compare?
Pleural fluid cholesterol > 45 mg/dL
Pleural fluid protein > 2.9 g/dL
How might you classify an effusion due to CHF as a transudate even if it meets normal criteria for an exudate and why?
Serum-pleural fluid albumin difference is >1.2 g/dL
Because protein is not truly leaking, serum is just relatively more concentrated due to diuresis in these patients
How do parapneumonic effusions (associated with pneumonia) typically resolve, and what is typical vs complicated?
Usually resolve spontaneously
Typical: pH>7.2, glucose >60, gram stain negative
-> not associated with loculation, Abx alone is fine
Complicated: pH <7.2, glucose <60, gram stain positive
-> chest tube and thrombolytics may be needed in addition as effusion becomes loculated
What are the criteria for calling an effusion an exudate: think protein and LDH
Any one of the following:
Pleural fluid protein is > 0.5 of serum protein
Pleural fluid LDH is >0.6 serum LDH
If no serum drawn: Pleural fluid is >2/3 upper limit of normal for serum LDH
Why is tension pneumothorax a medical emergency? How is it diagnosed?
Can cause low blood pressure due to decreased venous return
diagnosis generally by CXR
How can you tell if pulmonary hypertension is due to left ventricular disease or not? What are these two subsets of pulmonary hypertension called?
Pulmonary arterial hypertension (precapillary): If PCWP < 15 mmHg, LAP must not be elevated, and thus it is likely cor pulmonale
-> Group I (idiopathic or familial)
Pulmonary venous hypertension (postcapillary): If PCWP > 15 mmHg, LAP must be elevated, and thus it is likely due to LV disease
- > Group II
- > test for disease with ECG
What causes Groups III, IV, and V of pulmonary hypertension?
III - Lung diseases or hypoxia
-> test for disease with PFTs
IV - chronic
thromboembolism
-> treat with anticoagulants, surgical removal of PE’s, and Riociguat (nitric oxide mechanism)
-> test for disease with V/Q scan
V - multifactorial
What is the proposed pathogenesis of idiopathic pulmonary hypertension and the prognosis?
Imbalance of humoral mediators:
increased TXA2, endothelin, and 5-HT which vasoconstrict
Decreased prostacyclin and NO which vasodilate
This decreases luminal size of pulmonary arteries and eventually results in medial proliferation and right heart failure
- > survival is less than 2-3 years untreated
- > more common in women, intimal hyperplasia, medial hyperplasia, in situ thrombosis
What classes of drugs are used to treat Group I pulmonary artery hypertension?
Know everything on this
- Endothelin receptor antagonists (bosentan) - end of the line for boss man Stan
- PDE5 inhibitors (sildenafil, tadalafil)
- Guanylate cyclase stimulators (riociguat, also used for Type IV)
- Prostacyclin derivatives - i.e. think iLow to ePro! epoprostenol, iloprost
- DHP calcium channel blockers (rarely) - almost never works
What is viewed as basically the most clinically practical method for diagnosis of PE and what are its main drawbacks?
A contrast CT scan of the chest
Problems: Morbidly obese patients may not fit Renal insufficiency - contrast can put them in renal failure -> use V/Q scans Contrast allergy Dyspneic patients who keep moving Low sensitivity for very small PE's
What are classic signs of pulmonary hypertension?
Loud P2 due to high backpressure causing closing of the pulmonic valve to sound very loud.
Tricuspid regurg murmur may be heart if RV has dilated enough
Signs of right heat failure
What are the prophylaxis procedures for VTE in general surgery, orthopedic surgery, and medical patients who are very immobile (CHF, respiratory disease)
General surgery: moderate / high risk patients get UFH or LMWH
Orthopedic surgery: LMWH, fondaparinux, AND warfarin
Medical patients: Low dose UFH or LMWH (same as surgery)
What tests are used in the differential of PE to rule out other possible / likely conditions with these symptoms but will not definitively diagnose PE?
CXR - findings may be subtle or absent, but can rule out pneumonia or pnuemothorax
ECG - can rule out AMI or pericardial effusion. For PE, EKG would show tachycardia, and signs of RV strain
ABG - nonspecific, but if PaO2 >80, PE is unlikely
What are common and rarer side effects of UFH / LMWH outside of HIT?
Bleeding
Rarer:
Osteoporosis - due to stopping of bone deposition, think of bone sticking from tree with termites
Hyperkalemia - due to hypoaldosteronism
Elevated LFTs due to liver damage from metabolism of heparins - UFH only
What is the clinical presentation of HIT & its most common complication?
Drop in platelet count greater than 50% below baseline
Most common complication is venous thrombosis. Almost 50% will get DVT / PE if untreated.
Arterial thrombosis is less common. Arterial thrombosis can cause limb gangrene, skin necrosis, and organ infarction (MI, stroke).
What is the number one associated disease state with increasing INR and its mechanism?
Acute decompensated heart failure
-> decreased blood flow to liver decreases rate of metabolism of warfarin
How does the thyroid interact with INR?
Opposite of what you might think if you’re thinking of just blood flow
Hyperthyroidism - increased turnover of clotting factors -> increased INR (exaggerated effect of warfarin)
Hypothyroidism - decreased turnover of clotting factors -> reduced INR
What is the most important determinant of warfarin dosing, and what is the typical loading dose?
Patient’s age and diet
-> older people typically need a much lower dose because they have lower vitamin K stores and clotting factor proteins
Loading dose
-> does not exist. Once warfarin is added, inhibition begins and its just a waiting game (about 5 days). True steady state will be reached in a couple weeks.
How is warfarin reversal done emergently or if there is time?
Emergently - use prothrombin complex concentrate (PCC) with vitamin K IV
Slowly - use IV vitamin K, or PO vitamin K if you really dont care
What are the clinical uses of Fondaparinux?
Treatment of VTE (as bridge therapy until warfarin is therapeutic)
Prophylaxis of VTE post major orthopedic surgery
What is the only direct thrombin inhibitor taken PO? Why might it be the best of the DOACs? How does it differ from argatroban?
Dabigatran - has a reversal agent available
Differs from argatroban because it is renally cleared (vs argatroban = hepatic), and argatroban needs monitoring by PTT while dabigatran requires no monitoring
What is closing volume again?
The amount of air in the lung as the first airways begin to close -> will increase with aging because the airways begin to collapse at higher volumes. Effect is more prominent in the bases
What happens to spirometry with aging?
Decrease in FVC
Decrease in FEV1
Greatest decrease in FEF25-75
FEF25-75 = forced expiratory flow with 25%-75% of FVC remaining
What accounts for the V/Q mismatch in the elderly?
Earlier closure of small airways
- > base has poor ventilation but still good blood flow
- > V/Q is far less than 1 in the bases
- > extra air goes into apices instead -> V/Q will be far greater than 1
What are two overall causes of increased A-a gradient?
- Age
- Lung disease - hypoxemic respiratory failure
= pulmonary embolism, pneumonia, pulmonary edema
->anytime the PAO2 is staying the same but your PaO2 is dropping, the Aa gradient is increased. Thus, its really only hypoventilation and low environmental O2 which cause cause hypoxemic respiratory failure but not increase the A-a gradient
What equation describes the PaCO2?
PaCO2 is proportional to:
CO2 production rate / (minute ventilation * (1- dead space volume / tidal volume))
Based on the PaCO2 equation, what things can cause an increase in PaCO2?
Increased CO2 production - catabolic states and high caloric intake
Low minute ventilation - decreased respiratory drive
Dead space volume / tital volume ratio is high - respiratory diseases like COPD / asthma
-> hypercapnic respiratory failure
What are the symptoms of hypercapnic respiratory failure? What’s the treatment?
Somnolence, lethargy, headache, restlessness, slurred speech, asterixis, coma
Supplemental O2, and mechanical ventilation may be needed
What are some causes of low ventilation V/Q mismatch with widening of the A-a gradient? How does CO2 generally respond?
CO2 generally decreases or stays the same because ventilation is occurring fast enough to blow off CO2, but there is not enough gas exchange to allow total uptake of O2 (all around the lung)
- > diseases include pneumonia, atelectasis, pulmonary edema, COPD exacerbation, pneumothorax
- > upper portions of the lung blow off CO2, but lower portions fail adequate gas exchange
What are some common causes of right to left shunt?
ASD / VSD with Eisenmenger syndrome
Large arteriovenous malformations in lungs -> connections between pulmonary artery and veins
Basically your V/Q ratio is 0
What patient is in better shape:
- Patient has PaO2 of 70 mmHg on 100% oxygen
- Patient has PaO2 of 60 mmHg on 21% oxygen
- PaO2/FiO2 = 70/1.00 = 70
- PaO2/FiO2 = 60/0.21 = 300
Patient 2 is in a much better spot
What is the non-invasive ventilator which is probably better than putting an ET tube down most patients? When can it be used?
Non-invasive positive pressure ventilation (face mask)
-> do no need to be sedated, fewer complications, no intubation
Can be used in COPD, hypoxemic respiratory failure, neuromuscular disorders
When must an invasive mechanical ventilator be used for ARDS?
Small tidal volumes and prone ventilation
Mechanical ventilation must be used when patients cannot protect airway, are uncooperative, need restraints, are hemodynamically unstable, or have excessive excretions, do not improve to non-invasive PPV in first 1-2 hours
What is the most common type of primary insomnia?
Psychophysiologic Insomnia
- > disorder of high tension before going to bed from learned sleep-preventing associations
- > overly trying to fall asleep which is causing arousal
- > can sleep better on couch or away from home
What are the two opposing processes of the biologic clock?
Process S - homeostatic Sleep drive - builds throughout the day
Process C - Circadian arousal process - alerting effects of biologic clock. Opposes process S until the “off” biologic clock, which allows you to be very sleepy.
What is multiple sleep latency test and how is it useful for diagnosing EDS?
Measures tendency to fall asleep while lying in a quiet, dark bedroom at 4 times during the day
Normal daytime sleep latency should be greater than 15 min in well-rested adults, and no REM should occur in a 20 min nap
What cardiovascular morbidity is associated with OSA?
Hypertension
Metabolic syndrome: insulin resistance, HTN, proinflammatory state, oxidative stress, hyperlipidemia
Heart disease
CVA
What will narcoleptic patients show by polysomnography and MSLT?
Polysomnography - onset to REM less than 60 minutes
MSLT - sleep latency is <5 minutes, with 2 or more naps having REM onset within 10 min
What are the conservative measures to control OSA?
Weight loss, alcohol avoidance, sleeping on side, treatment of sinus congestion
What conditions are associated with RLS and why?
Iron deficiency (ferritin < 50) Renal insufficiency and pregnancy (low iron states) Parkinson's (low dopamine state)
Iron is required for production of dopamine, RLS is associated with low dopamine levels
