RES: Exam #3

transmural pressures in breathing

P1V1 = P2V2 or PxV = constant - an increase in volume leads to decrease in pressure (air comes in) - a decrease in volume leads to increase in pressure (air leaves) - at end expiration, outward recoil of the chest exactly counterbalances elastic recoil of the lung (= FRC) - inspiratory muscles contract to expand the chest -> lung volume increased -> pleural pressures more negative -> reduced alveolar pressure to below atmospheric pressure -> air drawn into lung

how to ask about tobacco

"Have you ever smoked cigarettes or used other tobacco products?" "Do you smoke every day, some days, or not at all?" "When did you last smoke?"

GPA histology, higher power

"a necrotizing, granulomatous, vasculitis"

Light's criteria

- (pleural fluid protein/serum protein) > 0.5 - (pleural fluid LDH/serum LDH) > 0.6 - pleural fluid LDH >⅔ upper limit of normal for serum LDH or >163 IU/L **presence of any of these indicates exudative fluid

large cell carcinoma of lung

- 10% of common carcinomas - undifferentiated (no specific lineage) - very aggressive

small cell lung cancer

- 13-15% of all cancers - exclusively in smokers - bulky, central tumor with extensive mediastinal lymph node involvement - rapid progression - associated with paraneoplastic syndromes (SIADH, Cushing's, cerebellar degeneration, Lambert-eaton, peripheral neuropathy, anorexia, weight loss) - 2-4 mo survival without treatment - responsive to chemo and radiation - limited stage (confined to hemithorax) or extensive (tumor beyond a radiation port and includes malignant pleural effusion usually) - treat with chemo, thoracic radiation, prophylactic cranial radiation for limited stage - chemo, immunotherapy, radiation to bone or brain mets for extensive stage

lung cancer symptoms

- 15% have none at dx - cough - hemoptysis - dyspnea - pneumonia symptoms - chest wall or bone pain - hoarseness - SVC syndrome - headache - weight loss, anorexia, fatigue

meconium ileus

- 15% of CF pts present with this at birth - obstruction of distal small intestine by meconium - associated with atretic segments of intestine treatment: enemas, surgery

adenocarcinoma of lung

- 20-40% of common carcinomas; most common primary lung cancer - most common carcinoma in non-smokers, but 80% occur in smokers - glands, mucin - more peripheral - irregular border of infiltration - in situ or invasive

lung cancer epidemiology

- 2nd most common cancer in the USA - most common in AA men - 75-80% of cases are NSCLCs - you see peak of lung cancers ~20 yrs following smoking (i.e. our nation saw peak in smoking incidence in 1990s but are just now expecting high incidence of cancers popping up)

CF treatments

- 3-4 hrs/day - pancreatic enzymes, CFTR modulators, airway clearance

small cell lung cancer (SCLC)

- 30% of lung cancers

normal cilia

- 9+2 microtubules - inner and outer dynein arms - radial spokes connect peripheral doublets to central singlets

PCD cilia

- 9+2 microtubules - no dynein arms - radial spokes connect peripheral doublets to central singlets

squamous cell carcinoma of lung

- 98% associated with smoking - may secrete PTH-like compound -> hypercalcemia - most occur centrally in bronchi, then larynx or trachea (think about smoking) - may have desmosomes, may make keratin pearls - can be spiculated (infiltrating) or cavitating

adenocarcinoma of lung in situ/bronchiolo-alveolar carcinoma (BAC)

- <3 cm lesion - "lepidic" growth pattern - adenocarcinoma hangs out on alveolar septae surface - mucinous or non-mucinous - unifocal or multifocal (particularly mucinous; must distinguish from mets)

bloody fluid from thoracentesis

- >100,000 RBCs/mm^3 - think cancer, pulmonary infarct, trauma, recent surgery - could be true hemothorax (actual bleeding into chest wall; hct will be >50%)

5 As of treating tobacco dependence

- Ask: identify and document for each patient at each visit - Advise: urger to quit in a clear, strong, personalized manner - Assess: is user willing to make an attempt? - Assist: use counseling and pharmacotherapy - Arrange: schedule follow-up or refer to someone

emphysema on CXR

- air trapping, destruction of alveolar septae, hyperinflation from loss of elastic recoil, frequent infections and mucus - increased AP diameter - flattened diaphragm - increased retrosternal clear space on lateral view

air bronchogram sign

- air-filled bronchi surrounded by fluid-filled alveoli - radiolucent branching structures

bronchiectasis treatment

- airway clearance up to 4x/day: exercise, airway hydration, percussion and postural drainage, cough, breathing techniques, various devices to shake the chest and assist with getting sputum out, albuterol inhaler, 7% hypertonic saline with DNAase - targeted antibiotics judiciously...PO, IV, inhaled (based on QOL, time to exacerbation, ability to walk)...IV are indicated for G- resistant organisms, when oral abx fail, if there is previous hx, if there is hemoptysis - airway hydration to thin mucus - bronchodilators - macrolides...3x/wk azithromycin can help with chronic Pseudomonas infection; also anti-inflammatory - vaccination, good general health, nutrition, rehab - surgery if disease is localized, non-progressive - transplant for severe cases

bronchiectasis CT

- airway dilation extends to periphery - permanent dilation of bronchi with peri-bronchial inflammation and organization

bronchiectasis bronchus, high power

- airway is very dilated, scarring in wall as well

asthma histology

- airways filled with mucus (blue) in lower L image - lots of inflammatory cells, hypertrophied smooth muscles, more mucus cells

pathophysiology of ILD

- decreased lung compliance - less volume inflation for the same pressure - reduced FVC - high FEV1/FVC (>0.75) - reduced FRC - reduced RV - diffusion impairment since barrier is thickened...this is really prominent during exercise (exercise-induced Hb desaturation)

UIP gross histology

- dense fibrosis - macroscopic fibrotic cysts - subpleural distribution in lower lobe - patchy normal parenchyma next to very fibrotic parenchyma - honeycombing - a fibrosing interstitial lung disease

predicted normal spirometry values

- derived from large studies of healthy, non-smokers, no hx of respiratory illness, heart disease, hazards, or abnormalities - age: absolute values increase in youth, decline in elderly - height: taller persons have greater absolute values - sex: healthy males and females of same age and height have different values - ethnicity: complicated and controversial

cor pulmonale

- destruction of pulmonary vascular bead -> increased pressure in pulmonary arteries -> R ventricular dilation and hypertrophy -> right HF with JVD, lower extremity edema

secondary prevention

- detects and cures disease in asymptomatic phase examples: Pap smear, hep C screening, fecal occult blood test

basic bronchiectasis pathology

- dilated airways, suppurative - lots of inflammation - bronchial wall destroyed - plasma cells, neutrophils, eosinophils - squamous metaplasia - ulceration into airway wall -> hemoptysis - bronchial artery hypertrophy

bronchiectasis gross histology (2)

- dilated bronchi (white arrows) reaching out into periphery - most likely developed from mucostasis -> colonization -> products like elastase and more inflammatory cells -> mucus hyper secretion, structural damage -> more mucostasis, irreversible dilation

decongestants: 2nd gen anti-histamines

- do not cross the BB-barrier as much - histamine is released from mast cells -> promotes capillary dilation and permeability in nasal mucosa via H1 receptors, promotes wakefulness in brain via H1 receptors - these anti-histamine will block H1 receptors in nasal area only - don't cause as much sedation Loratadine (Claritin) - Fexofenidine (Allegra) - Ceterizine (Zyrtec) -

speaking with patients about smoking

- don't lecture about statistics - focus on the health benefits of quitting 20 min: HR and BP drop few days: CO level drops within 3 mo: circulation and lung fxn improve within 1 yr: coughing and SOB decrease (cilia regain function) 1-2 yrs: risk of MI drops dramatically 5-10 yrs: risks of mouth, throat, laryngeal cancer is cut in half; risk of stroke decreases 10 yrs: risk of lung cancer is ½ that of someone still smoking 15 yrs: risk of CAD is near that of someone who never smoked

obstructive sleep apnea

- drive to breathe is present - transient obstruction of upper airway prevents inspiratory flow (from excess upper airway tissue...obesity, short neck, adenotonsillar hypertrophy in kids, or unknown cause) - inspiration muscles are active night symptoms: snoring, deranged sleep patterns day symptoms: hypersomnolence, headache, neuropsychiatric dysfunction

lung hyperinflation on CXR

- due to inability to exhale completely

diffuse alveolar hemorrhage

- dx by bronchoscopy - can come with Goodpasture syndrome, microscopic polyangiitis, granulomatosis with polyangiitis, lupus, cocaine

polysomnography

- dx of sleep apnea - measures EEG, EKG, BP< abdominal and chest expansion, air flow via canal, pulse ox apnea = >90% decrease in air flow for 10 sec hypopnea = reduction of airflow to degree that doesn't meet criteria for apnea apnea hypopnea index (AHI) = (apneas + hypopneas)/sleep time AHI > 15 is treated (is moderate, >30 is severe), AHI >5 with symptoms could be

clinical presentation of pleural effusions

- dyspnea - chest pain - cough - dullness to percussion - reduced or absent breath sounds CXR: flattened diaphragm, blunted costophrenic angles, contralateral mediastinal shift possible, meniscus sign ultrasound: lung may be compressed, can see diaphragm, air will be black space

acute PE symptoms & signs

- dyspnea - pleuritic pain - hemoptysis - apprehension, anxiety - syncope - tachypnea, hypoxemia, cyanosis - tachycardia, low BP, increased P2, JVD - edema, thrombophlebitis

effects of O2 and CO2 changes

- effect of high CO2 is greater when O2 is low - low O2 + high CO2 -> stronger, quicker response to increase ventilation - at high alveolar CO2 ventilation is already greater and the response to low alveolar O2 is quicker **carotid body really only kicks in when PO2 <60 - if alveolar O2 is reduced as alveolar CO2 increases, the combined effects are stronger than each one alone

classifying neoplasms by lineage

- epithelial (most common) - melanocytic - stromal - mesothelial

uses of spirometry

- evaluate dyspnea, determine if restrictive or obstructive disease - assess impairment severity in established lung disease - indicate prognosis - assess disease progression, treatment response - can objectively measure for disability evaluation - pre-surgical risk assessment - detects subclinical impairment - monitor adverse effects of environmental, iatrogenic, or occupational exposures

smoking cessation

- even greater benefit for women - risk will never get to the level of someone who never smoked, but is still very important - ask, advise, assess, assist - cessation -> slowed airflow obstruction decline, decreased lung cancer risk and other cancer risk, decreased CV disease

squamous cell carcinoma of the lung

- exclusively in smokers essentially - in central airways usually - cavitary lesions, obstruction of airways, distal atelectasis, post-obstructive pneumonia - hypercalcemia -> weakness, dehydration, mental status changes - clubbing

pulmonary HTN presentation

- exertional dyspnea - lightheadedness - fatigue - peripheral edema - weight gain - angina, syncope later - loud P2, ejection murmur, pulmonic insufficiency murmur, parasternal heave - possible right HF signs

emphysema gross histology (2)

- extensive dilation of alveoli, septal destruction - macroscopic air spaces - centrilobular emphysema likely; upper lobe...from smoking **increased anthracotic pigment indicates smoke exposure

compliance bias

- factors other than the screening test play a role in the better outcome seen among screened pts (adherent pts have better prognosis regardless of screening) - prevent this by comparing all outcomes with control group and screening group, regardless of compliance with the intervention...measure and just for healthcare access and utilization...randomize 2 groups

oil aspiration histology

- fat dissolved during prep

asbestosis histology, higher power

- ferruginous bodies

clinical presentation of lung vasculitides

- fibrosis - nodules of all sizes - consolidation or infiltrate - cavitation - pleural effusions - hemoptysis from DAH - pulmonary renal syndrome (renal failure + respiratory failure)...associated with glomerulonephritis and DAH secondary to an underlying autoimmune disorder

airspace disease on CXR

- fluffy, indistinct, hazy, air bronchograms - pneumonia - alveolar pulmonary edema - aspiration - drowning

pleural effusion on CXR

- fluid fills pleural space - mediastinal shift if large - removed silhouettes - loss of costophrenic angle - decubitus film will tell if effusion is free flowing or stuck in one place (loculated)

pneumonia on CXR

- fluid replaces air -> consolidation - lobar: Pneumococcus...air bronchograms, silhouette sign - bronchopneumonia: Staph. aureus...patchy, sometimes atelectasis, no air bronchograms - interstitial: Mycoplasma, Pneumocystis...interstitial -> airspace - round: Staph, Strep, influenza - aspiration: tend to be in R dependent areas - cavitary: Staph, Strep, reactivation TB

hypoxic vasoconstriction

- focal hypoxia (from pneumonia) -> upstream small arteries constrict - global hypoxia (from lung disease, altitude) -> diffuse constriction - also can be initiated by high CO2 - goal is to keep V/Q match image C = vasoconstriction to accomodate

mitigating tobacco cessation side effects

- for nausea or lightheadedness, reduce dosage - for irritability or cravings, increase dosage - for skin irrational, make sure pt is rotating site or applying cortisone first - for patch sleep disturbance, remove patch at night - for Chantix nausea, take with full glass of water and food - for Chantix sleep disturbance, take second dose earlier in day

glomus cells

- in carotid body - high O2 requirement - low O2 triggers cellular responses, along fenestrated capillary endothelium - senses changing arterial conditions, secretes neurotransmitters via hypoglossal nerve - sustentacular cells support them - sympathetic stimulation -> autonomic single -> contstriction of smooth muscle cells near glomus cell -> glomus thinks there is low O2

central sensors of breathing

- in ventrolateral medulla and raphe - mainly sense CO2 and H+; monitor CSF status - glia are primary sensors of low pH in CSF -> release ATP to stimulate adjoining neurons

non-small cell lung cancers (NSCLCs)

- includes adenocarcinomas, squamous cell carcinomas, large cell - clinically, histologically, molecularly heterogenous tumors - detection of driver mutations has aided in understanding biology and cancer therapy - different chemo than small cell lung cancers - 25-28% of advanced NSCLC pts overexpress PD-L1

CF manifestations

- liver and pancreas: plugging of bile ducts, exocrine failure, biliary cirrhosis - reproductive organs: infertility in men (no vas deferens), varies in women - bone: osteoporosis, osteopenia - sweat glands: salty sweat - GI tract: meconium ileus, gallstones, GERD, altered motility - respiratory tract: infection, inflammation, mucus, airflow obstruction

pneumotaxic and apneustic centers

- located in pons (pontine respiratory group/PRG) - not essential for normal respiratory rhythm but can modulate it pneumotaxic center - promotes rhythmic breathing apneustic center - causes gasping - prolonged inspiration + short expiration

restrictive lung disease spirometry and lung volumes

- low lung volume - shape of curve is the same since there is no obstruction (C in image) - lung volume changes depend on RLD type

pulmonary circulation pressures

- low pressure (25/5 mmHg) - low resistance (100 dyn*s/cmˆ5) - many capillaries can be recruited during exercise - low pulmonary artery pressures maintained - therefore, R ventricle is not equipped to handle higher pressures - lower lung zones are most greatly perfused and ventilated

supportive care for ARDS

- low tidal volume ventilation (decreasing size of people's breaths prevents over-engorgement; PEEP to keep alveoli open) - 6 cc/kg - allow a little acidosis to occur; "permissive hypercapnia" down to pH 7.15 - prone positioning (when prone, COVID pt can have most disease in posterior portions of lung where there is greatest perfusion...also you are overextending anterior portions)...do 16 hrs then 4 hrs spine

COPD CXR

- low, flattened diaphragm from lung hyperinflation - increased A-P diameter (air also between heart and chest wall)

low-dose spiral CT (LDCT)

- low-resolution image of entire thorax - low radiation exposure - very sensitive, can detect 2-3 mm nodules - grade B recommendation of annual screening for adults 55-80 for pts with 30PPY hx of smoking - soon, they will likely start at age 50 and do it for 20PPY hx of smoking

emphysema from α1-antitrypsin deficiency

- lower lobe more likely for panlobular pattern (global deficiency)...more from this α1-antitrypsin deifiencey - α1-antitrypsin comes from liver and counteracts elastase, so we have decreased anti-elastase activity result: elastic damage! leading to emphysema

pulmonary HTN: WHO group 3

- lung disease - hypoxic +/- hypercapnic vasoconstriction, sleep apnea, destruction of blood vessels by lung disease

pleural pressure

- lungs have natural tendency to collapse while chest wall has tendency to spring outward -> suction "negative pressure" (subatmospheric intrapleural pressure) between the pleural layers - Pip becomes even more negative (-8) during inspiration according to Boyle's law (since this space is closed and sealed from atmosphere)...this energy is transferred to the lungs (Ptp becomes more positive, Palv becomes -1) - the balance between collapse/spring out recoiling tendencies sets the functional residual capacity (FRC) volume

vasculitis associated with systemic diseases

- lupus - rheumatoid arthritis - sarcoidosis

total lung capacity (TLC)

- max amount of air the lungs can contain - sum of all non-overlapping lung volumes = RV + ERV + TV + IRV

pulmonary HTN

- mean pulmonary artery pressure (mPAP) >20 mmHG - normal mPAP should be 14 mmHg +/- 3 mmHg remember V=IR and ∆P=QR mPAP - L atrial P = CO x PVR mPAP = L atrial P + CO x PVR - so mPAP can be elevated when L atrial P is high, CO is high, or PVR is high

expectorant drugs

- mechanism of action unclear...may reduce mucus viscosity possibly by inhibiting parasympathetic stimulation of mucus secretion - clinical data do not show benefit Guaifenesin (Mucinex) - oral

leukotrienes

- mediate inflammation - lipid mediators derived from arachidonic acid - recruit immune cells, increase capillary permeability, can promote vasodilation and bronchoconstriction, can cause mucus cell metaplasia - LTC4 is particularly important for asthma pathogenesis

hamartoma gross histology

- mesenchymal lineage (looks like cartilage)

pancreatic insufficiency

- most common GI complication of CF - plugging of exocrine tissue -> destruction of gland -> decreased production of pancreatic digestive enzymes presentation: steatorrhea, malnutrition, vit ADEK deficiencies, weight loss treatment: enzyme replacement therapies, give vits ADEK - can lead to CF-related diabetes in 35-50% of CF pts...weight loss, lung function decline, death...β-cell dysfunction and islet destruction (loss of insulin secretion)...treat with insulin

regulation of CSF pH

- CSF enters from choroid plexus, drains via arachnoid villi; is a low-protein ultra filtrate of plasma - ions are generally impermeable to BB-barrier, but CO2 can diffuse freely - CSF is replaced every few hrs - has low protein content and decreased buffering power -> sensitive to changes in CO2 that ultimately result in changes in pH - central chemoreceptors sense low pH -> respiratory control center signal 0> increased ventilation to normalize the pH of the CSF - important for removing metabolic products from brain cells **CO2-retainers can change pH via bicarb management (secreting bicarb into CSF or renal compensation), but this takes a while and is complex...hypoexemia becomes main drive for ventilation **glia are primary sensors of low pH in CSF -> release ATP to stimulate adjoining neurons

D-dimer testing

- D-dimer is fibrin degradation product - elevated when recent thrombosis or in trauma, surgery, cancer, pregnancy, inflammation - use for pts with low likelihood of PE - <500 ng/mL = excluded PE - >500 ng/mL = need imaging

PE dx

- EKG - CXR (really to rule out pneumonia, pneumothorax) - arterial blood gas - D-dimer (to rule out for low likelihood) - V/Q scanning - CT with contrast (study of choice) = CT angiogram - pulmonary angiography (inject dye into R and L arteries then take images) - lower extremity Doppler **Wells criteria to determine low vs. high likelihood score

classification of COPD

- GOLD criteria classifies COPD as <80% FEV1/FVC - American Thoracic Society classifies as <70% FEV1/FVC - as you age, you lose a little lung function - to avoid over-diagnosing in elderly, you must look at lower limit of normal (LLN) value - full classification is based on degree of obstruction + symptoms and exacerbations

asthma treatment guidelines

- Global Initiative for Asthma (GINA) - USDHHS dx and management of asthma documents - have asthma action plans

alveolar hemorrhage syndromes

- Goodpasture's syndrome - acute lupus pneumonitis - granulomatous polyangiitis (Wegener's) 3 mechanisms: - auto-antibody to inherent antigen in basement membrane - auto-antibodies that bind antigens in circulation itself -> immune complexes that precipitate into small vasculature - ANCA auto-antibodies that bind to antigens within neutrophils and activate them -> innate immune response -> indirect damage to basement membrane ("pauci-immune")

pulmonary HTN: WHO group 2

- L heart disease - blood and pressure back up from L atrium into pulmonary arteries

cardiogenic pulmonary edema

- L ventricular pump failure or mitral valve stenosis - increased vascular markings on radiograph - venous and capillary congestion - increased free water in the interstitium and possibly alveoli

corticosteroids + β2 agonists (LABAs)

- LABA increases expression of the glucocorticoid receptor - corticosteroid increases expression of β2 receptor in bronchiole smooth muscle - so corticosteroids are synergistic with LABAs Advair (salmeterol + fluticasone) Symbicort (formoterol + budesonide) Dulera (formoterol + mometasone)

sarcoidosis presentation and dx

- Lofgren's syndrome: fever, hilar adenopathy, erythema nodosum...very high chance of resolution, use Tylenol only - dyspnea CXR: interstitial infiltrates around bronchovasculature - Stage I: hilar adenopathy, normal lung parenchyma - Stage II and III: adenopathy and abnormal parenchyma - Stage IV: fibrosis of upper lobes - can cause lupus pernio on skin, uveitis of eyes, dx: bronchoscopy, biopsy (dx if granulomas present neg. for TB, fungus, cancer) treatment: Prednisone for unremitting disease

asthma treatment

- Ma Huang stems and leaves contained ephedra ~2700 BC - controller inhaler: used daily to treat underlying inflammation...inhaled corticosteroids (ICS), ICS + LABA, leukotriene modifier (montelukast) • for severe disease: long-acting anti-muscarinics (ipratropium), phosphodiesterase inhibitors, monoclonal antibodies (Zolair subQ injection, some anti-IL-4 antibodies help with eczema too) - rescue inhaler: to relieve acute symptoms...albuterol sulfate (β-adrenergic agonist -> increased cAMP -> smooth muscle relaxation, bronchodilation) - spacer makes it easier for drug to be deposited into lung and not just oropharynx - nebulizer will convert medication into a mist; good in hospitals

bronchiectasis labs and results

- PFTs show airflow obstruction, trapping - changes on CXR or CT - leukocytosis or lymphocytosis - high sed rate - high C-reactive protein - anemia - serum IgE, ANA, α1-antitrypsin tests may help - sputum microbiology

COPD symptoms

- SOB - cough (dry or productive) - wheezing - fatigue - weakness - morning headaches or lower leg swelling (from poor gas exchange)

restrictive lung disease: abnormalities of chest wall

- TLC normal - reduced FRC - RV normal causes: morbid obesity (also reduced ERV), kyphoscoliosis, fibrothorax (after hemothorax or some trauma)

transudate vs. exudate

- Transudate: fluid buildup caused by increased hydrostatic pressure, decreased oncotic pressure, or increased negative Pip causing fluid to leave the vascular system - Exudate: fluid buildup from increased capillary permeability or lymphatic disruption due to inflammation or local cellular damage

adenocarcinomas of lung

- a NSCLC - most common NSCLC in the USA - in smokers and non-smokers - usually peripheral tumors, can arise in areas of previous scarring - associated with hypertrophic osteoarthritis (HPO = clubbing, long bone periostitis, arthritis) - may present with digital clubbing

late-onset (non-allergic) eosinophilic asthma

- a T2 high asthma - epithelium can secrete IL-33, IL-25, and TSLP in response to some irritant - these things act on ILC2 (innate lymphoid cells) cells (similar to TH2 cells) -> IL-5 drives eosinophilia - the ILCs produce very little IL-4 so don't really activate B-cells to make IgE (why this process is not "allergic")

pneumothorax

- air entering pleural space - from tear in lungs (blebs, bullae, high pressure ventilation, tall or thin males, bronchoscopy complication) - or from compromised chest wall (trauma, central line, lung biopsy) - symptoms depend on extent of pneumothorax and pt's clinical status - can have super deep costophrenic angle "deep sulcus sign" from chest wall being able to spring out unopposed - small pneumothoraxes can be observed, giving 100% O2 can help - chest tube for very severe cases tension pneumothorax: air escapes into pleura and positive pressure builds up as a one way valve...IVC can collapse from this if tension is not relieved via needle decompression followed by chest tube

allergic eosinophilic asthma

- a T2 high asthma - pt inhales an allergen (i.e. dust mite) - dendritic cells (DCs) extend a foot process into airway lumen, phagocytose the allergen - DC migrates to regional lymph node and presents to CD4+ T-cell - epithelium secretes TSLP, GM-CSF, IL-25, IL-33 to help with the DC and T-cell interaction - in the lymph node, the naïve T-cell differentiates into a TH2 cell -> secretes IL-4, IL-5, IL-13 - TH2 cell signals B-cell via IL-4 - the B-cells then class switch to make IgE - the IgE antibodies find mast cells and bind FCepsilonRI receptors; mast cell is ready now - if allergen is encountered again, the allergen cross-links two IgE on the mast cell -> degranulation (histamine, leukotrienes, cytokines) -> bronchoconstriction, vasodilatation, mucus production - TH2 cell secretes IL-5 -> promotes eosinophils to be released from marrow -> eosinophils degranulate to release inflammatory mediators - also TH2 makes IL-13 that induces goblet cell metaplasia and makes smooth muscle hyperresponsive

asthma-exacerbated respiratory disease (AERD)

- a T2 high asthma - triad of asthma, nasal polyposis, and aspirin sensitivity "Samter's Triad" - since NSAIDs block COX1 and COX2, arachidonic acid is shunted down leukotriene pathway - leukotriene pathway is hyper-active in AERD pts - leukotriene-receptor-antagonists may help with this

neutrophilic asthma

- a T2 low asthma - naïve T-cell differentiates into TH17 cell -> IL-17 -> CXCL8 -> neutrophilia in the airway - much more rare than eosinophilic asthma

acute PE

- a complication of venous thrombosis; vast majority orginate from lower extremity DVT - 5% develop chronic PE with chronic pulmonary HTN - 15-20% cause wedge infarcts - risk factors: age, immobilization, previous DVT, surgery, pregnancy, OCPs, malignancy, inherited thrombophilias consequences: increased alveolar dead space, hypoxemia, surfactant loss, atelectasis, hyperventilation, pulmonary infarction, significant decrease in cross sxnal area of pulmonary vascular bed -> acute right HF, systemic hypotension, shock, death

acute exacerbations of bronchiectasis

- a flare up of symptoms or departure from baseline - this increases symptom burden, reduced quality of life, social discomfort, healthcare utilization - people avoid social interactions - exacerbations take a while to dissipate (for many pts it takes a month)

pleurae & pleural space

- a potential space containing about 10 mL of fluid so surfaces can move against one another without friction - fluid is ultra-filtrate form capillaries (low protein, pH a little basic, <1500 total nucleated cells/mm^3...75% macrophages, 23% lymphocytes, 2% other cells) should be formation/resorption balance (refreshing but not accumulating) - visceral and parietal pleurae are thin membranes lined by mesothelial cells - blood vessels and lymphatics are beneath these layers - fluid is vascular transudate + mesothelial secretions coming from chest wall systemic microcirculation, exits via lymphatic stomata of parietal layer (between mesothelial cells) - normally, you drain 0.4 mL/kg/hr but you can do 20 mL/hr if needed - visceral layer fed by bronchial arteries, drains into pulmonary veins - parietal layer fed by intercostal arteries, drains systemic - no pain fibers in lung, just irritant receptors - response to irritant receptor activation is cough - there are pain fibers in the parietal pleura

pneumoconiosis

- a type of ILD - from coal exposure or other inorganic matter - nodules in upper lobe; can coalesce to form massive fibrosis

asbestosis

- a type of ILD - from mechanic work, railroads, construction - small fibers in periphery of lower lobes - see ferruginous bodies on biopsy

silicosis

- a type of ILD - from mining, ceramics, quarry working - small nodules in central portion of upper lobes on CT ("simple silicosis") - eggshell calcification of lymph nodes

COVID-19 common presentations

- abnormal CT - lymphocytopenia - fever, cough, SOB - 10% of pts report diarrhea/nausea 1-2 days before other symptoms - 84% of cases mild, 10-15% severe, 5% critical - 39% of pts with comorbidities have severe illness on admission - 3.4-29% of cases become ARDS - 1-8% of cases become shock - 1-7% of cases become ARF

COPD epidemiology

- about 16 million people in USA have COPD but estimate 14 million more are undiagnosed - 65 million cases worldwide - 3rd leading cause of death usually, 2nd leading cause of disability - only 20% of smokers get it however - 70% are younger than 65 - female mortality greater - most prevalent in tobacco-growing states or those with low SES - 80-90% of USA cases are due to cigarette smoking - in low SES countries, biomass fuels are #1 cause - also could be from hyper-responsive airways, occupational factors, α1-antitrypsin deficiency (only genetic cause known) - can be exacerbated from weather and temp changes

acute respiratory disease syndrome (ARDS) defined

- acute (<1 wk) - bilateral infiltrates - arterial PO2/FiO2 <300 - not due to HF - etiology: direct or indirect pulmonary insult - treatment: supportive critical care (low tidal volume ventilation) + treating underlying etiology - recognizing ARDS changes care

mucinous or non-mucinous adenocarcinoma

- adenocarcinoma subtype - more common in women and individuals who have never smoked - cough, dyspnea, bronchorrhea (frothy sputum) - dense infiltrate with air bronchograms

Goodpasture syndrome

- affects young adult males most - diffuse alveolar pattern radiologically - anti-basement membrane type IV collagen IgG antibodies damage basement membranes - linear IgG deposition - anti-glomerular basement membrane IgG can be detected in serum

bronchiectasis overview

- affects ~200,000 in USA but prevalence is increasing and we estimate more like 500,000 - 6-10 clinics in USA - prevalence skewed toward elderly with many cases >75 yo; more common in Asian/Pacific Islanders - non-TB mycobacteria (NTM) infection may confound the issue...difficult to tell which came first, infection or bronchiectasis - women affected a little more than men

COVID-19 disease severity associations

- age - comorbidities (hospitalizations 6x higher, death 12x higher) - race/ethnicities (Hispanic > black) **overall fatality rate ~1% but 10-20% if >70 yo **comorbidities for COVID = CV disease, chronic lung disease, diabetes, CAD **60% of Americans have >1 comorbidity, 42% have multiple

pneumothorax on CXR

- air trapped in pleural space - can be spontaneous, traumatic, from decreased compliance, or from pulmonary interstitial emphysema - no lung markings visible - deep sulcus sign if supine - do inspiratory/exp. radiographs if subtle, decubitus radiograph, CT

obstructive lung disease

- all about exhaling - takes longer to expire completely - remember normal FEV1/FVC is >80% - dx: low FEV1/FVC (<70% predicted) - reduced FEF25-75% - severity is based on the FEV1 - increased compliance - scooped out flow rate /volume curve - lower peak flow in flow rate/volume curve 1) asthma 2) COPD (bronchitis or emphysema subgroups) 3) bronchiectasis **ACO = asthma/COPD overlap - airflow is reduced by functionally decreased caliber of airways (from inflammation, mucus plugging, hyperactive smooth muscle contraction) - premature airway collapse - air flows in easier than it flows out - expiration becomes active - increased R can be overcome by increasing pleural pressures to be more neg. during inspiration and more pos. during expiration - higher lung capacity (increased TLC) - more air remains in lungs after normal or forced expiration (increased FRC and maybe RV) - decreased VC **PFCs tell you they are obstructed, hx will tell you what type it is

restrictive lung disease

- all about inhaling...requires compliant chest wall, normal inspiratory muscle strength (diaphragm), compliant lung parenchyma - fibrosis: fibroblast infiltration -> lung CT thickens -> stiff lung, low compliance (difficult inflation, forceful deflation) - normal FEV1/FVC - low VC - decreased compliance - lower peak flow in flow rate/volume curve

thoracentesis

- allows you to dx transudative vs. exudative in 75% of cases - also helps with dyspnea (allow lung expansion) but degree of relief will depend on how quickly their disease progressed - need >1 cm on ultrasound - CT-guided can help with tricky cases - usually enter posteriorly, enter right above a rib above diaphragm

asthma radiology (if done)

- alternating atelectasis and over expansion

severe pulmonary edema histology

- alveolar space filled with protein-poor fluid

bronchiectasis defined

- an obstructive disease of the airways - clinical syndrome of cough (usually lots of sputum, waxes and wanes over time, constitutional symptoms often too like fatigue, anorexia, weight loss) - pathologic dilatation of airways, lack of tapering, thickening of bronchial wall - pockets collect mucus and pus easily - many causes (i.e. CF, others more common) - irreversible and incurable, but manageable and generally not life-shortening

COPD defined

- an obstructive disease of the airways - preventable and treatable - airflow limitation is not fully reversible - limitation is progressive - associated with an enhanced abnormal inflammatory response of the lungs to noxious particles or gases - produces significant systemic consequences • chronic bronchitis (producing sputum regularly) OR • emphysema (damage to alveoli) ALSO **must have abnormal spirometry with evidence of obstruction • asthma (little more rare)

asthma defined

- an obstructive disease of the airways; most common disease of tracheobronchial tree - characterized by: • airway inflammation • reversible airflow obstruction (via meds) • airway hyperresponsiveness

constrictive bronchiolitis

- an obstructive lung disease of more distal airways; fibrosis of small airway walls - can be from exposure to sand storms or fire pit burnings - seen in soldiers

antitussives: opioid receptor agonists

- an opiate that 1) on presynaptic neuron will bind µ receptor to inhibit Ca2+ influx and so no neurotransmitter is released, and 2) on postsynaptic neuron will bind µ receptor to increase efflux of K+ -> hyperpolarization - often combined with promethazine Codeine

immune complex small vessel vasculitides

- anti-glomerular basement membrane disease (Goodpasture's) - cryoglobulinemic vasculitis - IgA vasculitis - Hypocomplementemic urticarial vasculitis (C1q vasculitis)

pleuritis

- any inflammatory process involving the parietal pleura - pain fibers are in this pleura - signficance depends on clinical setting

asbestosis histology

- asbestos is a fibrogenic dust - rigid fibers get into distal airspaces and enter interstitium -> patchy, subpleural fibrosis - nodules in lower lung lobes

assessing patient about tobacco cessation

- ask open-ended questions to gather insight on readiness and their thoughts about quitting "What are your thoughts about stopping or cutting down?" "What do you not like about smoking? What do you enjoy about smoking?" "What would be different in your life if you no longer smoked?" **1 PPD is $188/mo or >$2,000/yr

finding tobacco triggers

- ask your patients so you can identify triggers automatic smoking comes with: drinking coffee, boredom, driving, being around others, being stressed or anxious, breaks at work, talking on phone, when consuming alcohol

Cheyne-stokes respiration

- associated with CNS issue, HF, or first being at high altitude - abnormal breathing pattern of tachypnea then hyperpnea in crescendo-decrescendos - basically abnormal feedback from peripheral and central chemoreceptors - example: small dip in CO2 -> apnea - system overshoots negative feedback

short-acting β2 agonists (SABAs)

- asthma treatment - used for rescue therapy for acute symptoms - last <12 hrs **some β1 cross-reactivity -> tachycardia, angina, A-fib, HTN, prolonged QT...generally not major concerns Albuterol/Salbutamol - inhaled prn...1300x more potent for β2 **can desensitize β2 receptors (via PKA phosphorylation or down-regulated via receptor degradation)...reversible Epinephrine - 1:1 β1/β2 ratio for selectivity...high cardiac toxicity risk

cigarette

- at least 69 of 7,000 chemicals in a cigarette are carcinogenic

CFTR gene

- at position 7q31 - discovered in 1989; Francis Collins (current NIH director) worked on the team - for ATP-gated transmembrane regulator of Cl-; regulates Cl- secretion in the lung and Cl- absorption in the sweat glands - ∆F508 is common severe mutation, autosomal recessive where carriers are unaffected - 1/25 carrier frequency in Caucasians, 1/100 carrier frequency in African Americans - >2000 mutations have been identified in the same gene (allelic heterogeneity) - poor correlation between class of mutation and degree of lung disease, but good correlation between mutation class and the pancreatic disease

Curschmann spirals

- in asthma - mucus casts

effort-dependent phase of forced expiration

- at the beginning of expiration, lung volume is high, airway diameter is greatest and the airways offer low resistance to airflow - pressure inside the airway decreases gradually along its length from the alveoli to the mouth - air flows outward due to elastic recoil, accelerated by high Pip - when the internal airway pressure is higher than the surrounding pressure, (positive Ptp) the airways stay open - the "equal pressure point", where airway transmural pressure is 0 (marked with a "z"), is located in the large cartilaginous airways, which resist collapse...flow increases with increasing effort

clinical signs of bronchiectasis

- audible secretions - sputum inspections - finger clubbing (not from hypoxia or COPD!) - crackles - wheezes - skeletal abnormalities: tall, thin, pectus excavatum, scoliosis - situs inversus (and PCD) - respiratory failure

α1-antitrypsin deficiency

- autosomal recessive - 1/5,000 incidence - presents <40 yo with lower lobe-predominant emphysema - loss of function mutations in both allele of SERPINA1 (protease inhibitor) gene at 14q32 - 12 alleles associated with lung or liver disease...most severe is Z allele Glu342Lys...genotype PI-ZZ - Z protein aggregates in rough ER of hepatocytes -> serum α1-antitrypsin 15% of normal, neutrophil elastase inhibition is only 20% of normal - staining hepatocytes will show entrapped α1-antitrypsin

COPD signs

- barrel chest - accessory muscles for respiration - wheezing - "tripod" (to support chest wall) - decreased breath sounds - lower extremity edema (from cor pulmonale)

ARDS classification

- based on arterial PO2/FiO2 ratio mild = 200-300 = 27% mortality moderate = 100-200 = 32% mortality severe = <100 = 45% mortality

squamous cell carcinoma in situ histology

- basement membrane is keeping the neoplasia in check

how to advise about tobacco

- be strong and clear about benefit of quitting tobacco use, "Quitting all tobacco use is one of the most important things you can do for your health" - be empathetic, "I understand that quitting can be difficult and I'm here to support you" - offer help, "we have effective resources such as medications and the Quitline to help you succeed" - be open to patient, "I'd like to hear your thoughts about stopping or cutting back on your smoking"

decongestants: α1 agonists

- bind α1 receptors to induce vasoconstriction in mucous membranes -> reduced nasal mucous membrane swelling - also can treat hemorrhoids (drug in Preparation H) - recall that vasculature has α1 and β2 receptors Pseudoephedrine Phenylephrine

varenicline (Chantix)

- blocks nicotine receptors but still triggers some dopamine release - decreases pleasure of smoking (since receptors are blocked) when pt smokes - common side effects: nausea, insomnia, headache, vivid dreams - contraindicated for severe renal impairment, pregnant or breastfeeding, pts <18 yo

consolidation on CT

- blood vessels not seen through the ground glass area

ground-class on CT

- blood vessels seen through ground glass area - indicates active inflammation in ILD (would be responsive to immunosuppressants)

pharm for asthma and COPD

- both involve inflammation and constricted airways - asthma: mast cells, eosinophils, TH2 cells...hyper-responsive bronchioles -> respiratory obstruction - COPD: neutrophils, macrophages, CD8+ T-cells...fibrosis of small airways -> respiratory obstruction - can treat chronic inflammation with anti-inflammatories - can treat constricted airways with bronchodilators

mixed sleep apnea

- both obstructive and central sleep apneas

non-neoplastic airway diseases (for histology lectures)

- bronchiectasis - asthma - chronic bronchitis (part of COPD) - emphysema (COPD)

PDE4 inhibitor drugs

- bronchiole smooth muscle cells are regulated via acetylcholine, adenosine, epinephrine -> contraction - recall that β2 receptor for epi has an intracellular portion that produces cAMP that converts to AMP via PDE4 Roflumilast - PDE4-selective inhibitor Theophylline - adenosine antagonist, PDE4 inhibitor (caffeine does this too)...also has anti-inflammatory effects like stimulating IL-10 release, inhibiting inflammatory gene transcription, apoptosis of eosinophils and neutrophils, activation of histone deacetylase **seizures and other neuro, arrhythmias, GI symptoms...therapeutic index = 2 so tough to avoid toxicities

dx of primary lung tumor

- bronchoscopy (excellent for bronchial lesions; transtracheal or transbronchial needle aspiration) - transthoracic needle biopsy (excellent for peripheral lesions) - video-assisted thoracoscopic biopsy - thoracentesis (for pleural effusions associated with cancer)

mesothelioma histology, low power

- can appear "sarcomatoid"

bupropion SR (Wellbutrin, Zyban)

- can attenuate weight gain during treatment, help patients with concomitant depression, low cost - common side effects: headache, dry mouth, insomnia, weight loss - contraindicated for low seizure threshold patients, pregnant

small cell carcinoma of lung

- cancer of smokers - 20% of common carcinomas - common paraneoplastic syndromes (SIADH -> hyponatremia) - commonly present at high stage (very aggressive) - responsive to chemo and radiation, but low 5-yr survival - malignant neuroendocrine cytology, no nucleoli, high mitotic activity and necrosis - usually central and involving mediastinal lymph nodes (think smoking) - note alternation of high proliferation and necrosis

length-time bias

- cancers detected by screening are often slower growing and less aggressive - survival appears better in this group but it isn't due to screening - prevent this with an RCT (randomizes slow-growing disease and aggressive disease in the groups)

smoking and lung cancer

- carcinogens in tobacco smoke = nitrosamines, benzopyrene, polycyclic hydrocarbons - 15% of US adults smoke - any level of smoking hx, particularly long-term, increases risk - American Indians and Alaska natives smoke 2x more than the rest of the USA - adults with HS degree have 8x higher rate of tobacco use - 25% of individuals living below poverty line smoke; 14% of those living above it smoke

mucolytic drugs

- reduces disulfide bonds to degrade mucin - free sulfhydryl group on drug will cleave S-S bonds N-acetylcysteine - inhaled

peripheral sensors of breathing

- carotid bodies and aortic bodies - sense changes in blood O2, CO2, and pH (only small response to CO2 and pH) - major sensors of low O2; increase firing when arterial PO2 <60 mmHg to increase ventilation - afferent fibers of the carotid body join with the glossopharyngeal nerve to carry signals to the brain carotid body: - highly metabolically active glomus cells (high O2 requirement, low O2 triggers cellular responses, along fenestrated capillary endothelium, senses changing arterial conditions, secretes neurotransmitters via hypoglossal nerve, sustentacular cells support them, sympathetic stimulation -> autonomic single -> contstriction of smooth muscle cells near glomus cell -> glomus thinks there is low O2)

mucinous adenocarcinoma of lung histology

- cells attempting to form glands to line alveoli

endogenous lipid pneumonia/golden pneumonia/ post-obstructive pneumonia

- central major airway obstruction - peripheral infiltrates with or without central mass - increased #s of foamy macrophages, with or without cholesterol clefts, without foreign material...those macrophages cannot exit due to the obstruction

assisting patient with tobacco pharmacotherapy

- cessation meds support patients in making behavior change by decreasing withdrawal symptoms like craving, irritability, depression - encourage use by all patients attempting to quit, unless contraindicated - meds triple quit rates 1) nicotine replacement therapy (NRT): patch, gum, lozenge, oral inhaler, nasal spray 2) varenicline (Chantix) 3) bupropion SR (Wellbutrin, Zyban) - standard-of care is 12 wks of combination NRT (short acting + long acting) OR 12 wks of varenicline (Chantix)

pulmonary HTN: WHO group 4

- chronic thromboembolic pulmonary HTN - thrombus obstructs vessel lumen

silhouette sign

- classic finding on CXR of pneumonia - structures appear to disappear because fluid is next to them

spine sign

- classic finding on CXR of pneumonia - bottom of spine appears more dense than upper on lateral view

pulmonary HTN: WHO group 1

- clear epidemiological connection to pulmonary arterial HTN - early vasoconstriction of smooth muscle - thickening of arterial walls, decreased size of vessel lumen - endothelial dysfunction and intimal fibrosis, vascular SM proliferation, in situ thrombosis, inflammation, plexiform lesion (emanate from vessel layers around obliterated arteries) causes: idiopathic pulmonary arterial HTN, heritable, drug or toxins, CT disease, portal HTN, CHD, HIV, schistosomiasis

coal pneumoconiosis histology

- coal (inert dust) deposits in lung interstitium around bronchovascular bundles - "coal dust macules"

atelectasis on CXR

- collapsed lung - fissures displaced, affected lung is more dense - other lung may be more inflated - structures displaced TOWARD effected lung - can be sub segmental, compressive, or obstructive

lung metastases

- common site for metastasis since lung receives blood volume continuously - multiple nodules, multiple lobes, multiple lungs...whereas primary lung cancers come in 1 mass - can be carcinomas (breast, GI, renal, head or neck squamous cell) - can be sarcomas (osteosarcoma, soft tissue sarcoma) - can be melanomas - tend to be well-circumscribed - metastasis is the most common malignancy of lung

pulmonary edema on CXR

- commonly accompanies left HF - fluid in interstitium -> fluid in alveoli - also can come from ARDS

acute lupus pneumonitis

- component of systemic lupus erythematosus (SLE) - affects child and adult females more - diffuse alveolar pattern radiologically - auto-antibodies to variety of antigens in circulation -> immune complexes cause necrotizing capillaritis - granular IgG deposition - ANA or anti-dsDNA antibodies detectable in serum

lead-time bias

- condition is found earlier by screening, but actual time person would have died isn't changed - "survival time" is longer but person isn't better off - prevent this with an RCT (measuring "morality rates" rather than "survival time")

ventral respiratory group (VRG)

- contains inspiratory and expiratory neurons - neurons project to phrenic nerve, intercostal neurons, abdominal motor neurons - contains pre-bötzinger complex (BC) (site where normal breathing rhythm originates) - contains nucleus ambiguous (NA), nucleus para-ambigualis (NPA), and nucleus retroambigualis (NRA)

dorsal respiratory group (DRG)

- contains inspiratory neurons - receives many sensory inputs from peripheral respiratory receptors; main sensory nucleus - some neurons project directly to motor neurons that control respiratory muscles - contains the nucleus tracts solitarius (NTS)

asthma presentation

- cough - chest tightness - expiratory wheezing - dyspnea - prolonged expiratory time - enlarged nasal turbinates, pale or inflamed mucosa, eczema (want to check for general allergy signs) - serious: decreased breath sounds, accessory muscle use, intercostal retractions

granulomatosis with polyangiitis (Wegener's)

- cough, hemoptysis, pleuritis - treatable with cyclophosphamide and steroids - multifocal nodular infiltrates, possible cavitation radiologically - pauci-immune: ANCA antibodies bind antigens in neutrophils -> innate immune response damages basement membrane - c-ANCA in >85% of pts with active disease - elastin stain can help find disrupted vessels

decongestants: 1st gen anti-histamines

- cross the BB-barrier - histamine is released from mast cells -> promotes capillary dilation and permeability in nasal mucosa via H1 receptors, promotes wakefulness in brain via H1 receptors - these anti-histamines will block H1 receptors in nasal area; will induce drowsiness from the brain H1 effect Diphenhydramine (Benadryl) Promethazine (Phenergan)

lupus pernio

- cutaneous sarcoid lesions

COPD: DL-CO and ABG

- damaged alveoli prevents gas exchange - DL-CO is a lumped constant of factors that affect gas diffusion across alveoli (surface area, barrier permeability, Hb status, body position, exercise) - since virtually all CO in the blood is bound to Hb, the plasma PCO is ~0...DL-CO = derived constant/alveolar PCO - COPD pts retain CO2 - blood gas = pH, CO2, O2, calculated bicarb

high resolution chest CT (HRCT)

- very useful for dx of ILDs - detects disease that is sub-radiographic on chest X-ray - can suggest a specific dx - can help distinguish between active inflammation and fibrosis

what spirometry measures

- forced vital capacity (FVC): volume between TLC and RV in a forced expiration **reduced FVC is a hallmark of restrictive disease; can be followed longitudinally; still need to determine absolute lung volume **need plethysmography or helium dilution to determine RV - forced expiratory volume 1st sec (FEV1): volume expired during first sec in a forced expiration; correlates with functional capacity **reduced FEV1 and FEV1/FEV ratios are hallmarks of obstructive disease; FEV1 correlates with prognosis - forced expiratory flow (FEF25%-75%): average flow rate during middle half of the expiration

EGFR mutation

- found in 16.6% of lung cancer patients - more frequent in women, individuals who have never smoked - reported in adenocarcinoma of the lung in 81% of cases - large-scale screening possible

DAD: proliferative/organizing phase

- from ARDS - >1 wk after identifiable lung injury - decreased pulmonary compliance requiring mechanical ventilation; 50% mortality - interstitial pattern more than alveolar - interstitial and intra-alveolar fibroblastic proliferation in sites fo fibrin accumulation - temporally uniform

diffuse alveolar damage (DAD): exudative phase

- from ARDS - identifiable lung injury 0-2 wks before - acute dypsnea, hypoxemia, decreased compliance - patchy ground glass on CT - begins with endothelial or epithelial injury -> type II pneumocyte hyperplasia -> proteinaceous edema -> fibrin deposition from coagulation

asthma dynamic hyperinflation

- gas trapping occurs and lungs hyperinflate -> higher intrathoracic pressure at end-expiration -> decreased venous return since R atrium cannot fill - pressure is built up in alveolus - auto-peep from ventilator (pt does not have time to exhale) -> decreased RV preload -> cardiogenic shock -> death - so shut off ventilator if this is happening! decreased respiratory rate will let lungs deflate

ARDS resolution

- get rid of protein, reabsorb fluid - or collagen can be laid down

antitussives: centrally-acting glutamate antagonists

- glutamate is involved in the neuronal signaling in the brain respiratory center - this drug antagonizing Glut binding -> brain cannot sense irritant and stimulate cough muscles Dextromethorphan (main drug in Robitussin) **potential for abuse...dissociative affects at high doses (amnesia, derealization, depersonalization, identity alteration, identity confusion)

US Preventive Services Task Force

- grades based on strength of evidence and balance of benefits and harms of the preventive service - A, B, C, D, I

benign lung neoplasms

- hamartoma (mesenchymal) - squamous papillomas (epithelial; trachea and larynx) - pleomorphic adenoma (epithelial salivary gand analog)

assisting patient with managing tobacco triggers

- hard candy, cinnamon sticks, toothpick, sunflower seeds - puff on cut-up plastic straw - walk, exercise - practice mindfulness, spirituality, relaxation techniques - puzzle, coloring - call someone - leave the triggering situation - put cigarettes in trunk when driving - make home 100% smoke free - brush teeth after meals discuss the strategy: If _____ happens, then I will do _________

pleural fluid cell count

- high neutrophils suggest acute inflammatory process - eosinophils >10% indicate air etiology, blood etiology, parapneumonia, drugs, asbestos, exposure, parasites - >50% lymphocytes suggests malignancy or TB...also could be post-CABG, chylothorax, yellow nail syndrome, chronic rheumatoid effusions, sarcoidosis - glucose <40 suggests parapneumonic effusion or empyema, rheumatoid disease, malignancy, TB - LDH >1000 suggests complicated parapneumonic effusion, malignancy - triglycerides indicates chylothorax - amylase indicates pancreatitis, esophageal rupture

asthma epidemiology

- highest prevalence in developed countries - hygiene hypothesis? immune system isn't given opportunity to develop response to microbes - 30,000 ppl/day have asthma attack, 5,000 ppl/day visit ER in USA

usual interstitial pneumonia (UIP) histology

- histology seen with idiopathic pulmonary fibrosis (IPF) of interstitium - affects adults, mean survival 3-5 yrs, poor response to steroids - patchy fibroblastic and fibrotic foci alternating with normal parenchyma in lower lobes...bouts of fibrosis starting at different time points - "temporally and spatially heterogenous" - honeycomb change (macroscopic peripheral airspaces surrounded by fibrosis) CXR: patchy, subpleural infiltrates....blurry costophrenic angles

Starling forces

- hydrostatic capillary pressure favors filtration while colloid oncotic pressure favors reabsorption (increased in distal capillary) - hydrostatic interstitial fluid pressure favors reabsorption while colloid oncotic pressure of interstitial fluid favors filtration fluid movement = filtration coefficient [(Pc - Pis) - oncotic permeability x (COPc - COPis)] edema (fluid entering lung interstitia) can result from: - increased capillary permeability (ARDS, O2 toxicity, toxins) - increased capillary hydrostatic pressure(pulmonary HTN, excess IV fluids, high CVP) - decreased plasma oncotic pressure (protein starvation, liver failure reducing albumin, proteinuria, blood dilution by IV fluids) - other (tumor inhibiting pulmonary lymphatic drainage, lymphatic blockage)

Starling forces in pleural space

- hydrostatic pressure gradient of capillary is greater than that of pleural space, favoring net filtration (small influx of fluid into pleural space) - oncotic pressure gradient favors reabsorption - hydrostatic pressure gradient is greater so this requires lymphatic drainage

keratin pearl histology

- hyperchromatic cells around pearls - indicates squamous lineage - ability to see outline of squamous cells indicates the intercellular bridges

spirometry in clinical practice

- important for dx - provides objective, reproducible measures of respiratory mechanics - detects abnormalities from COPD, asthma, interstitial lung disease - key tool to gauge treatment effects and clinical trials of new therapies **used to promote a racist agenda in the past (compare lung function of enslaved to owners) equipment: volume device (directly measures changes in volume and time, flow is derived), flow device (directly measures flow, volume is derived) process: pt maximally inhales then forcefully exhales (>6 sec); need >3 maneuvers with no defects; largest FVC and FEV1 must not differ more than 5% between maneuvers

charcot-leyden crystals

- in allergic asthma where eosinophils degranulate and granules precipitate out in sputum to form crystals

acute response to O2 deprivation or high CO2

- increased amplitude and frequency of ventilation - hyperventilation (carotid body response) decreased end tidal CO2 results from the stimulated ventilation - when O2 is given back, there is sudden apnea until O2 and CO2 re-equilibrate, then ventilation is stimulated again - this has been seen in dogs and humans alike - acute exposure to high CO2 -> gradual increased amplitude and frequency of ventilation but takes a little while because CO2 has to get into the CSF first (relatively slow equilibration of CSF pH) **note there is wide variation in O2-deprived ventilation response in different people

emphysema pathology

- increased elastase activity -> septal destruction, dilation of distal airspaces -> alveoli rupture and enlarge -> decreased surface area available for gas exchange

exudative effusion

- inflammatory, proteinaceous, cellular fluid - from increased capillary and pleural membrane permeability - or pleural disease - or obstruction of flow in lymphatic channels causes: - pneumonia - malignancy - PE - GI disease

aspiration

- inhaling something into lung - foreign bodies in children, gastric acid or food for adults (mineral oil laxatives or nasal drops -> exogenous lipoid pneumonia) - focal alveolar pattern, typically R lower lobe - gastric acid aspiration -> DAD, foreign body -> giant cell reaction

corticosteroids for asthma or COPD

- inhibit expression of pro-inflammatory cytokines - increase expression of anti-inflammatory lipocortin/annexin-1 -> inhibition of phospholipase A2 Beclomethasone - inhaled Triamcinolone - inhaled Flunisolid - inhaled Fluticasone - inhaled Budesonide - inhaled Mometasone - inhaled Solumedrol - IV Predisone - oral toxicities: - thrush, pneumonia for mild to moderate asthma pts on inhaled drug - various for severe asthma pts on oral systemic drug

antitussives: peripherally acting Na+ channel blockers

- inhibits signaling of sensory neurons in respiratory system - blocks Na+ channels that depolarize in those neurons -> no signal is ever sent to brain that irritant is present Benzonatate (Tessalon) - prescription oral Lidocaine Lignocaine

signs and symptoms hinting at types of bronchiectasis

- insidious onset of cough, late middle age -> idiopathic - infectious episode in the past -> post-infectious - neonatal respiratory problems, otitis, sinusitis -> PCD - organ laterality -> PCD - recurrent pancreatitis, pancreatic insufficiency -> CF - GI disease -> CF or Crohns - infertility -> CF or PCD - Mycobacteria or aspergillus -> NTM or ABPA then bronchiectasis

antibody drugs for asthma and COPD

- interfere with activation of eosinophils and mast cells

interstitial lung disease (ILD)

- interstitium = space between pulmonary capillary and alveolus - looks like small, thin lines on CT - also called diffuse parenchymal lung disease (DPLD)

small cell carcinoma of the lung, gross histology

- irregular, solid mass - central - hilar node metastasis - associated with SIADH from ADH secretion by tumor -> hyponatremia

common tobacco withdrawal symptoms

- irritability, frustration, anger, restlessness, impatience - anxiety - difficulty concentrating - cravings, urges to use - depressed mood - insomnia - increased appetite, weight gain **most manifest within 1-2 days, peak within week 1, subside within 2-4 wks

basic cough mechanism

- irritant irritates epithelia -> neuronal receptors in bronchioles activated -> signal sent to respiratory center of the brain -> cough muscles are stimulated to expel the irritant

diagnosis of bronchiectasis

- is cough productive, when did it start, is there fatigue, are there frequent infections, what color is sputum, CT diseases, comorbidities - timeline is critical - is there asthma, family hx, reflux, infertility, childhood illness - lung CT = gold standard causes: idiopathic, post-infectious, Crohns or other systemic diseases, COPD, bronchial obstruction, inhalation of toxic gases, immunodeficiencies, ABPA, CF or other defect of mucociliary clearance - identifying cause is important for choosing specific treatment - treating underlying cause can prevent disease progression, allow genetic counseling for families, and help the patient's peace of mind and acceptance image = primary ciliary dyskinesia

silicosis gross histology

- large fibrotic nodules in parenchyma - color variation suggests pigment deposit after inhalation exposure - middle and upper lobe distribution

mucinous adenocarcinoma of lung in situ histology

- large mucin vacuoles on top of epithelia on alveolar septae

effort-independent phase of forced expiration

- later in expiration - as lung volume and airway caliber decrease...airway R increases - P is dissipated faster when R is high (steep pressure drop) - EPP migrates toward alveoli, small airways dynamically collapse - airway pressure now falls below the surrounding pressure in the small, non-cartilaginous portion of the airway (negative Ptp gradient) -> collapse -> even higher R **think of sucking too fast through a floppy straw -> collapse - flow becomes effort independent and is driven mainly by elastic recoil of the lung

bronchiectasis and CF

- leading cause of morbidity and mortality in CF - progressive airflow obstruction -> respiratory failure symptoms: dyspnea, cough, sputum production, intermittent infectious exacerbations treatment: abx, airway clearance, CFTR modulators

leukotriene inhibitors

- leukotrienes are synthesized by mast cells and eosinophils -> bind LT receptors on bronchiole smooth muscle cells -> constriction, plasma exudation, mucus production - so these drugs are for those subsets of asthma Zileuton - inhibits 5-lipoxygenase Montelukast - inhibits leukotriene binding its receptors (antagonizes) Zafirlukast - inhibits leukotriene binding its receptors (antagonizes)

inhalation of drug

- limits cardiac toxicities, but doesn't eliminate them - only about 5% of inhaled dose gets to lung...tiny amount may cross into circulation from here...mucociliary clearance could bring some drug back to mouth and then you swallow - 95% ends up being swallowed...now it is essentially an oral drug -> some amount becomes systemic and can access heart to produce toxicities

residual volume (RV)

- volume remaining after a maximal expiration - determined by plethysmography or gas dilution

sarcoidosis

- most common ILD of young adults - affects African American females more severely - driven by macrophages, DCs, lymphocytes that form tight, well-formed non-caseating granulomas (no central necrosis; accumulation of epithelioid histiocytes) - antigen taken up by DC -> peptide presented to CD4+ T-cell -> T-cell activation and TH1 cytokine activation -> granuloma formation -> resolution or fibrosis - granulomas can secrete 1α-hydroxylase -> catalyzed hydroxylation to make vit D active -> decreased renal Ca2+ excretion and increased GI Ca2+ absorption -> hypercalcemia -> nephrocalcinosis possible - granulomas can secrete ACE as well - non-TB Mycobacteria and Propionibacteria indicated as antigenic TH1 cytokines more prominent: IFN-γ, IL-2, IL-12

asthma airway remodeling histology

- mucus cell hyperplasia - basement membrane thickening - smooth muscle hypertrophy - edema - increased eosinophils - thickened intra-luminal mucus

chronic bronchitis histology

- mucus cell hyperplasia - mucus gland hyperplasia

asthma: airway inflammation

- mucus on far L, then inflammatory cells in airway wall, far R is airway cartilage

lung metastasis gross histology

- multifocal, central and peripheral - well-circumscribed masses - mets are more common than primary lung and brain cancers

adenocarcinoma in situ gross histology

- multifocal, fuzzy borders

other ventilation sensors

- muscle spindles in diaphragm and intercostals send signals about ventilation status - muscle and tendon spindles and mechanoreceptors in joint capsules and ligaments respond to work or exercise - pain and temperature receptors cause gasp and stimulation of ventilation - inputs from many of these terminate in the dorsal respiratory group (DRG) - proprioception important for allowing body sense that breathing is matching need

small cell carcinoma of lung histology

- neuroendocrine cytology = looking like watercolor - very limited cytoplasm - lots of mitosis occurring

Ondine's curse

- newborns breathe fine when awake but cannot during sleep - associated with PHOX2B gene - a central sleep apnea

tobacco chemistry

- nicotine makes up 1% of smoke...85% absorbed in lung (= 1 mg IV) - gases like CO, CO2, acrolein, methanol, phenol, pyrenes, formaldehyde, anthracenes - particulates like resin cores (50% deposited on and cleared by cilia, remainder by phagocytosis and lymphatic transport)

central sleep apnea

- no drive to breathe during apnea episodes (no signal coming from respiratory center) - inactive respiratory muscles

silicosis histology, low power

- nodular hyalinized fibrosis - mid to upper lung zones

lung masses and nodules

- nodule = <3 cm - mass = >3 cm - benign tend to be calcified, smooth margin, no change over weeks (changing in days only...more infectious probably) - malignant tend to be >5 cm, change over weeks or months - follow with CT

innate lymphoid cells (ILCs)

- non-T or B effectors cells - cause non-allergic eosinophilic asthma - react to epithelial-derived cytokines TSLP, IL-25, IL-33 - secrete IL-5 (drives eosinophilia), IL-13 (drives mucus cell hyperplasia and smooth muscle hyperresponsiveness) - lack antigen-specific receptors - produce very little IL-4 so don't really activate B-cells to make IgE

transudative effusion

- non-inflammatory fluid, low protein content - from increased hydrostatic pressure - or decrease in plasma colloid oncotic pressure - or movement from the peritoneal space (from ascites) - clear, straw-colored, non-viscid, odorless usually causes: - CHF - PE - cirrhosis - nephrotic syndrome - peritoneal dialysis - SVC syndrome

formation of squamous cell carcinoma

- normally, Strat. squamous epithelium is in oral cavity - smoking -> pseudostratified respiratory epithelium is injured -> metaplasia to Strat. squamous epithelium to tolerate smoke (still well-organized, polarized maturation) -> more smoking -> dysplasia to squamous cell carcinoma in situ (disarray, no maturation)

PE infarcted tissue histology

- note acellularity

gross histology of squamous cell carcinoma of lung

- note anthracotic pigment

invasive squamous cell carcinoma histology

- note keratin pearls

small cell carcinoma of lung histology (2)

- note nuclear molding

normal alveolar septae, transmission EM

- note tight junctions in bottom image

small cell carcinoma, high power

- nuclear molding = nuclei very close to each other **remember HSV can do this too!

obstructive bronchiectasis

- obstruction (tumor or something) -> mucus cannot be expectorated -> bacteria grow, inflammation, tissue destruction from microbial products like elastase -> mucus hypersecretion, bronchiectasis

turbid fluid from thoracentesis

- orange or milky fluid suggests chylothorax (thoracic duct injury) - gross pus indicates an empyema

hypersensitivity pneumonitis/extrinsic allergic alveolitis histology

- organic antigens (hay, sugarcane, maple bark, hot tubs, bird proteins, feathers, plastics or rubber manufacturing) inhaled via occupational or environmental exposure - affects bronchovascular stroma; patchy peribronchiolar and interstitial chronic inflammation; loosely-formed granulomas in inflammatory background (many lymphocytes) - pts present with low-level dyspnea, cough, fatigue (more subacute response) CXR: bilateral interstitial linear or nodular pattern

cryptogenic organizing pneumonia (COP) / bronchiolitis obliterates with organizing pneumonia (BOOP)

- organizing fibrosis of small airways and interstitium - usually idiopathic; multiple associations - can cause obstruction or restriction on PFTs - patchy airspace infiltrates radiologically - subacute presentation with cough, dyspnea, fever, malaise treatment: immunosuppression (usually Prednisone)

mechanisms of pulmonary HTN

- passive (WHO group 2): high L atrial pressure (diastolic HF, systolic HF, mitral stenosis, mitral regurgitation, etc) - hyperdynamic: high flow state (high CO) from ASD, AV fistula, cirrhosis, anemia, etc - occlusive (WHO group 4): PVR elevation from chronic PE, tumor - obliterative (WHO group 1): PVR elevation from pulmonary arterial HTN (idiopathic, heritable, drug induced, CT disease, HIV, CHD, schistosomiasis, chronic CCB use, PPHN), emphysema, ILD, sarcoidosis - vasoconstrictive (WHO group 3): PVR elevation from hypoxemia, high pCO2 problem: obstructive disorder of pulmonary vasculature -> increased PVR -> pulmonary HTN -> increased R ventricular work -> cor pulmonale

cystic fibrosis (CF) overview

- patients are living longer (mean survival in the 40s) - ~30,000 pts alive in USA - >50% living with CF are adults - 240 transplants done at UNC, 6 have lived over 20 yrs - lung function continues to improve...employment, marital status, eduction continue improving

adenocarcinoma of lung gross histology (2)

- peripheral, unifocal mass - solid, large, multilobulated - usually smokers

chylothorax

- pleural fluid accumulation due to disruption of thoracic duct from trauma or tumor - dx by pleural triglycerides >110

diffuse bronchiectasis

- post-inflammatory, non-obstructive - examples = CF or PCD abnormal mucus or abnormal ciliary function -> mucus cannot be expectorated -> bacteria grow, inflammation, tissue destruction from microbial products like elastase -> mucus hypersecretion, bronchiectasis

primary ciliary dyskinesia (PCD)

- predisposes one to CRS and sinus surgery need - autosomal recessive genetic defect -> abnormal or absent ciliary beat as cilia lack dynein arms - 15,000 pts in USA - associated with chronic sinusitis, bronchiectasis, pneumonia, recurrent otitis media, reduced fertility in women, sterility in men, situs inversus (50% of pts) - neonatal respiratory distress, chronic daily wet cough from birth - special form = Kartagener syndrome: triad of situs inversus, nasal polyps (sinusitis), bronchiectasis *ciliary movement must be synchronized during the gastrula stage if correct sidedness of the body is to result --> situs inversus with this disease* **a random phenomenon

RDS of newborns

- premie babies - tachypnea, intercostal muscle retraction, hypoxemia - diffuse alveolar filling pattern with air bronchograms - insufficient surfactant production -> atelectasis -> hypoxia/acidosis -> epithelial necrosis - diffuse intra-alveolar hyaline membrane formation too (exudative DAD)

hamartoma

- presents from adolescence to adulthood - not congenital - benign, primary neoplasms from mesenchymal lineage (cartilage, fat in excess and disarray) in the stroma - solitary, lobulated, cartilaginous - more peripheral - popcorn calcification

primary prevention

- prevents disease from occurring at all examples: immunizations, smoking cessation, seat belt use

COPD: V/Q mismatch

- primary problem in COPD - airway obstruction or damaged alveoli -> poor gas exchange - poor ventilation but still have circulation (very low V/Q ratio)

treating pulmonary arterial HTN

- prognosis was terrible 25 yrs ago, ~3 yrs median survival - we know pts are deficient in NO and prostacyclin, high in thromboxane and endothelin-1 - if pt has acute vasodilator response (>10 mmHg decrease), then treat with CCBs - if pt doesn't respond to acute vasodilator: increase NO with oral drug (Sildenafil, Tadalafil, Riociguat), increase prostacyclin (Epoprostenol - IV, Treprostinil - various, Iloprost - inhaled, Selexipag -oral), decrease endothelin with oral drug (Bosentan, Ambrisentan, Macitentan) - diuretics, O2, anticoagulants, surgical thromboendarterectomy, atrial septostomy, lung transplant

nicotine replacement therapy (NRT)

- provide nicotine without toxic or carcinogenic agents - available for free through the Quitline - minimal side effects with proper use - flexible dosing and gradual reduction (patch can be 7 mg, 14 mg, 21 mg) - attenuates weight gain side effects: - patch: long-acting (provides consistent, low-level stimulation of nicotine receptors, reduces intensity of urges but triggers still come)...skin irritation, nausea, dizziness, insomnia - gum: short-acting (helps manage trigger urges)...nausea, headache, mouth soreness...only chew for 3-40 min - lozenge: short-acting (helps manage trigger urges)...nausea, headache, mouth soreness - oral inhaler: short-acting (helps manage trigger urges)...throat irritation, cough - nasal spray: short-acting (helps manage trigger urges)...nasal and thought irritation, runny eyes, rhinorrhea, cough **cigarette brings huge amount of nicotine to brain within minutes -> dopamine **max dose is 42 mg patch + 4 mg gum/lozenge

COPD and chronic hypoxemia

- pt at risk of developed right HF from lung disease (cor pulmonale) - these pts have worse edema and CO2 retention

acute bronchitis

- pts that is producing sputum - 9th most common outpatient illness; affects 5% of adults in USA - #1 reason for antibiotic abuse in the United States - sudden onset of cough >5 days and averages 18 days - no fever, tachycardia, or tachypnea - may have mild obstruction on spirometry - 90% are of viral origin - hx will help you determine if this is acute bronchitis or chronic bronchitis

blue bloater vs. pink puffer

- pure chronic bronchitis pt just has airway obstruction - this leads to poor CO2 exchange and cardiac issues -> HF -> lower extremity edema, retain more CO2 "blue bloater" - pure emphysema pt just has more damaged alveoli - this leads to decreased O2 exchange and hypoxemia -> thin appearance "pink puffer"

V/Q scanning

- radio-labeled technetium for perfusion, radio-labeled xenon gas

mesothelioma

- rare malignancy of the pleura - associated with asbestos exposure - deeply invasive growth pattern - epithelial, spindle cell, or biphasic - radiologically: diffuse pleural involvement, loss of costophrenic angle, - causes pleural thickening, tumor, exudative pleural effusion **benign pleural plaques can be in pleural space, are not malignant, but come from asbestos exposure

restrictive lung disease: weak inspiratory muscles

- reduced TLC - FRC normal - increased RV causes: polio, myasthenia gravis, guillain-barré syndrome, ALS

restrictive lung disease: abnormalities of lung parenchyma

- reduced TLC - reduced FRC - reduced RV causes: sarcoidosis, idiopathic pulmonary fibrosis

obstructive sleep apnea complications

- respiratory acidosis or hypoxemia on blood gas - 2º polycythemia from increased EPO - pulmonary HTN -> cor pulmonale or R heart hypertrophy - HTN - CAD - arrhythmias - HF - stroke - diabetes, insulin resistance - nonalcoholic fatty liver disease **screen using STOP-Bang questionnaire (snoring, tiredness, observed apnea, high BP, BMI, age, neck, gender) treatment: weight loss, position, less alcohol, less sedatives, oral appliance, upper airway surgery, tracheostomy, hypoglossal nerve stimulation - positive airway pressure: very efficacious, CPAP or BiPAP

central controller: brainstem respiratory nuclei

- respiratory control center is located in the medulla - 2 areas = dorsal respiratory group (DRG) and ventral respiratory group (VRG) DRG - contains inspiratory neurons - receives many sensory inputs from peripheral respiratory receptors; main sensory nucleus - some neurons project directly to motor neurons that control respiratory muscles - contains nucleus tractus solitarius (NTS) VRG - contains inspiratory and expiratory neurons - neurons project to phrenic nerve, intercostal neurons, abdominal motor neurons - contains pre-bötzinger complex (BC) (site where normal breathing rhythm originates) - contains nucleus ambiguous (NA), nucleus para-ambigualis (NPA), and nucleus retroambigualis (NRA)

interstitial disease on CXR

- reticular or nodular, sharper, more discrete - interstitial pulmonary edema - fibrosis - metastasis - sarcoid

pacemaker model of breathing

- rhythmic electrical activity in the pre-bötzinger complex drives rhythmic breathing via spontaneous depolarizations that are then relayed to hypoglossal nuclei - this rhythm is then relayed to the breathing muscles via the hypoglossal nerves - ablation of pre-Bötzinger complex -> inhibition of rhythmic breathing **muscles of tongue, nares, pharynx are "respiratory" since during forceful inspiration they dilate upper airway passages

asthma: eosinophils

- see in mild, moderate, and severe asthma - recruited by TH2 cells or ILCs - steroid-responsive - infiltrate airway wall where they release cytokines, lipid mediators, peroxidase, ROS -> amplified inflammatory response, more airway hyperresponsiveness, more airway remodeling

asthma: neutrophils

- seen in severe asthma - recruited by TH17 cells - steroid-resistant - infiltrate airway wall where they release cytokines, lipid mediators, peroxidase, ROS -> amplified inflammatory response, more airway hyperresponsiveness, more airway remodeling

pulmonary HTN dx

- signs of R ventricular hypertrophy on EKG - large pulmonary arteries or lung disease signs on CXR or CT - assess R heart size, pulmonary artery pressure, L ventricular fxn on echo (Doppler can measure degree and pressure of regurgitation through tricuspid valve) - R heart cath is necessary for dx (mPAP >20 mmHg, wedge pressure <15, PVR >240) - check for obstructive or restrictive lung disease on PFTs - V/Q scan (go to) or pulmonary angiography (higher index of suspicion) to check for chronic pulmonary emboli - HIV, autoimmune testing labs - polysomnography to check for sleep apnea

silicosis histology

- silica is a fibrogenic dust - silicotic nodules in central portions of mid to upper lung zones - early nodules are full of macrophages and fibroblasts - late nodules are large, acellular

COPD lung volumes

- since you lose elastic recoil of alveoli, chest wall can pull outward more - FRC increases - TLC increases (hyperinflation) - tidal volume increases - increased RV (can't exhale as much with forced exhalation)

NSCLC staging

- size - involvement of lymph nodes - metastasis

ANCA-associated vasculitides

- small vessel vasculitis - microscopic polyangiitis (p-ANCA), MPO antibodies - granulomatosis with polyangiitis (Wegener's), PR3 antibodies...c-ANCA - eosinophilic granulomatosis with polyangiitis (Churg-Strauss), think asthma...p-ANCA

COPD pathogenesis: vicious cycle

- smoking -> impaired mucociliary clearance, bacterial colonization... - exposure + genetic predisposition -> COPD - right now, we don't know the genetic predisposition - inflammatory cells activate both innate and adaptive immunity - inflammation that occurs leads to: 1) small airway remodeling and fibrosis 2) alveolar wall destruction 3) mucus hypersecretion

COPD treatment

- smoking cessation will help them do better longterm - best is not to ever smoke! - smoker loses lung fxn at 60 cc/yr while non-smokers lose it at 10-15 cc/yr - 46 million people still smoke - smoking = leading preventable cause of death - start short-acting bronchodilators when symptoms begin - add regular long-acting bronchodilators at stage II - add inhaled steroids at stage III - add long-term O2 at stage IV GOLD guidelines: I: FEV1 80% II: FEV1 50-79% III: FEV1 30-49% IV: FEV1 <30% A: asymptomatic, not many exacerbations B: persistent symptoms - add long acting β-agonist (LABA) and/or long acting muscarinic antagonist (LAMA) C: more symptoms - LABA + LAMA and add inhaled steroids D: even worse - LABA + LAMA + steroids and add roflumilast or macrolide - pulmonary rehab helps - surgery or lung transplant to replace the damaged tissue (lung volume reduction surgery results in a lung with better elastic recoil)

lung cancer risks

- smoking, 2nd hand smoke - pollution (esp. adenocarcinoma of lung), asbestos (likely tumor promoter) - radon, cadmium, uranium, arsenic, nickel, polycyclic hydrocarbons, silica - family hx, genetic predisposition - previous hx of cancer - COPD, lung fibrosis - being female (leading cause of cancer death in women; women smokers more likely to develop adenocarcinoma than men) - race

asthma: airway hyperresponsiveness

- some obstruction in baseline asthma - but if asthmatic pt breaths in an irritant (cold air, perfume, smoke, methacholine, pollen, pets, exercise, fungal spores, pollution, stress or anger), it will contract even further **methacholine is muscarinic receptor agonist used to test for asthma

bronchiectasis viscous circle

- something causes impaired sputum clearance - bacterial colonization results - this leads to chronic inflammation and tissue damage - now we have further impaired sputum clearance **many therapies target points in this cycle!

functional residual capacity (FRC)

- volume remaining in lungs after tidal expiration = ERV + RV - important for dx of lung diseases - defines the point of mechanical equilibrium between lung recoil vs. rib recoil - at end of tidal expiration with open glottis and no airflow, Palv = 0 - cannot be measured with typical spirometry; can use plethysmograph (best way to measure lung volumes) or helium dilution (not as accurate in pts with obstructive diseases)

idiopathic pulmonary fibrosis (IPF)

- specific form of chronic fibrosis interstitial pneumonia limited to the lung - associated with histology appearance of usual interstitial pneumonia (UIP) (sub pleural, lots of collagen deposition) - injury to airway epithelium -> GF release -> fibroblasts differentiate into myofibroblasts -> collagen deposited - characteristic HRCT findings (lower lobes, subpleural honeycomb cysts, minimal ground glass) - can cause "traction bronchiectasis" - finger clubbing - most common ILD of older adults - most common idiopathic interstitial pneumonia

malignant lung neoplasms - epithelial (carcinomas)

- squamous cell - adenocarcinoma - large cell - small cell neuroendocrine

mast cell stabilizing drugs

- stabilizes mast cells, prevents release of mediators Cromolyn

acute PE treatment

- standard or LMW heparin - Warfarin after - direct oral anticoagulants - thrombolytic therapy for massive PE with hemodynamic compromise - surgical embolectomy or catheter-based techniques...rarely done - IVC filter

reducing mortality in COPD

- stop smoking - giving hypoxic pts O2 will help if they are <80% sat - lung volume reduction surgery in the right patient **not inhalers we give!! these only treat symptoms

volume-time curve in asthma

- takes longer to get air out due to obstruction (low FEV1 but normal FVC) in mild to moderate disease...both FEV1 and FVC could be reduced in severe disease - bronchodilator will normalize

screening

- testing for a health problem or risk factor when there are no recognized signs or symptoms - goal is to help people live better or longer - risk lead-time, length-time, compliance biases

pleural effusion treatment

- therapeutic thoracentesis - chest tube drainage (thick fluid) - pleurodesis for recurrent effusion (no more potential space) - tunneled small bore catheter (PleurX) for regular drainage

asthma diagnosis

- to check reversible airflow obstruction: spirometry pre- and post-bronchodilator (albuterol) - want to see >12% improvement...or use a peak flow meter to determine variability - to check airway hyperresponsiveness: methacholine challenge test - want to see 80% of normal FEV1...only done if dx couldn't be made with spirometry or peak flow meter! - to check airway inflammation: exhaled NO (increased with eosinophilic inflammation), induced sputum (showing eosinophils, charcot-leyden crystals, Curschmann's spirals, creole bodies)...not used as much

tertiary prevention

- treatment of disease itself to reduce complications examples: treating diabetes, treating lung cancer to prevent metastasis, PT/OT/SLP after stroke

short-acting M3 antagonists

- treats asthma, COPD - used for maintenance therapy to prevent acute asthma symptoms - can last >12 hrs if needed - M1-M5 selectivity **inhibits rest and digest functions Ipratropium - oral, qid

IL-5 antibody drugs

- treats eosinophilic asthma Mepolizumab - IL-5 antibody Benralizumab - IL-5 receptor antibody

lymphatic spread of metastasis to the lung

- tumor tracks along lymphatic vessels

squamous cell carcinoma of lung gross histology (2)

- univocal, cavitating lesion with necrotic core - central - associate with hypercalcemia from PTHrP secretion by tumor

squamous cell carcinoma of lung gross histology

- univocal, irregular, solid mass - central - bronchial obstruction and hilar nodal involvement

bronchiectasis etiology

- unknown in >50% of pts - often a distant event (necrotizing pneumonia, recall bias is an issue) - often present as misdiagnosed asthma, chronic bronchitis, COPD, chronic cough, where no sputum has ever been collected

emphysema from smoking histology

- upper lobe more likely for centrilobular pattern (irritant present in localized area)..more from smoking - α1-antitrypsin comes from liver and counteracts elastase - smoking decreases α1-antitrypsin and increases elastase activity result: elastic damage! leading to emphysema

approach for treating COPD

- use more anticholinergic drugs

long-acting M3 antagonists

- used for maintenance therapy to prevent acute asthma symptoms - can last >12 hrs if needed **inhibit rest and digest functions (are anti-parasympathetics...xerostomia, dry nasal membranes, constipation, tachycardia, urinary retention) Tiotropium - M3 selective, inhaled qd Aclidinium - M3 selective, inhaled bid Umeclidinium - M3 selective, inhaled qd Glycopyrronium - M1-M5 selective, inhaled bid

long-acting β2 agonists (LABAs)

- used for maintenance therapy to prevent acute asthma symptoms - can last >12 hrs if needed **some β1 cross-reactivity -> tachycardia, vasoconstriction, angina, A-fib, HTN, prolonged QT...generally not major concerns Salmeterol - inhaled bid for asthma or COPD... 85,000x more potent for β2 Formoterol - inhaled bid for asthma or COPD...120x more potent for β2 Indacaterol - inhaled qd for COPD...1.5x more potent for β2, high cardiac toxicity risk - always used in combination with inhaled corticosteroids...LABAs alone may increase risk of death from asthma

DL-CO in asthma

- usually normal or even elevated - could be from increased volume of pulmonary capillary blood from the hyperinflated lungs - higher Hb correlates to higher DL-CO

large cell carcinoma histology

- variation in nuclear size and shape, high nuclear cytoplasmic ratio, prominent nuclei, multiple mitotic figures

pulmonary HTN: WHO group 5

- varied disorders - sarcoidosis, myeloproliferative disease, renal failure, others

ventilation response to exercise

- ventilation can increase significantly during exercise, but this is not due to O2, CO2, or low pH - stimulus for increasing ventilation during exercise is not well-understood - once anaerobic threshold is reached, pH begins to drop -> ventilation increases even more, arterial O2 increases, arterial CO2 decreases

asthma lungs on autopsy

- very hyperinflated - heart and main vessels are not visible

ARDS pathophysiology

- ways to keep homeostasis at alveoli: oncotic proteins (draw fluid into vascular lumen), interstitium (can remove fluid as needed), alveolar epithelium tight junctions - inflammatory response at alveoli -> tight junctions broken down (TNF-α, CXCL8, neutrophils, oxidants) -> fluid and protein enter alveoli -> alveolar collapse because surfactant is overwhelmed -> gas exchange lost, increased lung density (harder to breathe) - hyaline membranes form (proteinaceous debris clogging alveoli) 1) edema phase 2) hyaline membrane phase 3) interstitial inflammation and fibrosis

COPD pathogenesis: elastase

- we all have elastin in our airways and alveoli - elastase degrades this constantly to keep us from getting sick, and meanwhile α1-antitrypsin stops elastase to protect our alveoli - so if you are deficient in α1-antitrypsin, elastase is unchecked - smoking or infection can recruit neutrophils which will release elastase

sarcoid granuloma, high power

- well-defined - histiocytes and multinucleate giant cells - associated with bronchovascular bundles along lymphatic routes

tobacco dependence

- you've made >1 unsuccessful quit attempts - average attempts = 7 - you experience withdrawal symptoms when trying - you keep smoking despite awareness of health risks - you require more tobacco to feel satisfied - you give up social activities

COPD and exercise

- you've moved your FRC up and you are breathing at a higher level (static hyperinflation) - when you add exercise and respiratory rate increase, gas trapping and hyperinflation occurs even more and it is very uncomfortable (dynamic hyperinflation) - very reduced inspiratory capacity (IC)

bronchiole smooth muscle receptors

- β2 receptors: agonists induce relaxation - M3 receptors: antagonists induce relaxation **methacholine can be used to test for asthma remember; would never be theurapeutic!

overview of ventilatory control

1) central controller: pons, medulla 2) effectors: respiratory muscles (autonomic and voluntary control compete through spinal motor neurons) 3) sensors: central chemoreceptors (medulla), peripheral chemoreceptors (carotid bodies, aortic bodies), lung receptors, other receptors - the system changes ventilation to rectify deviations from normality that are detected by the sensors - classic negative feedback - Galen of Pergamon discovered that nerves control muscles

asthma-COPD overlap (ACO) diagnosis

1) persistent airflow limitation on spirometry despite adequate administration of short-acting bronchodilator in subjects >40 yo 2) "significant" hx of smoking or equivalent lifetime exposure to biomass 3) physician dx of asthma before 40 yo

pneumoconiosis histology

= dust in the lungs - reaction to inorganic antigens (usually mineral dusts) encountered via occupational or environmental exposure - fibrogenic dusts: silica (silicone dioxide), asbestos - inert dusts: coal

invasive adenocarcinoma of lung

>3 cm overall diameter or >0.5 cm invasive - multiple architectural patterns...lepidic pattern, acinar pattern - glandular cells, mucin production

alveolar hemorrhage syndromes - immunofluorescence

A: using anti-IgG antibody in nephron...note linear deposition B: note immune complexes deposited in basement membrane C: no direct IgG with basement membrane involvement...ANCA antibodies interacting with neutrophils

mediastinal shift on CXR

AWAY from process: - pleural effusion - pneumothorax TOWARD the process: - obstructive atelectasis - pneumonectomy

diseases that mimic ILD

congestive HF - rule this out with hx and physical exam - CXR would show cardiomegaly, Kerley B lines, pulmonary edema, effusion possible

cancer-immunity cycle

cytotoxic lymphocyte antigens (CTLAs) can be bound by anti-CTLA antibodies to down regulate the immune response

what is the most common ILD of young adults?

sarcoidosis

organizing DAD histology

spindled fibroblasts proliferating in interstitium

normal WBC percentages

Neutrophils: 40% to 60% Lymphocytes: 20% to 40% Monocytes: 2% to 8% Eosinophils: 1% to 4% Basophils: 0.5% to 1% Band: 0% to 3%

IgE antibody drugs

Omalizumab - targets IgE and takes them out of commission

IL-4 antibody drugs

Dupilumab

peribronchovascular stroma and pulmonary interstitium

stroma = tissue in alveolar septae interstitium = CT around bronchovascular bundle...contains lymphocytes, lymphatic vessels

causes of pleural effusions

transudative (non-inflammatory fluid, low protein content): - from increased hydrostatic pressure - or decrease in plasma colloid oncotic pressure - or movement from the peritoneal space (from ascites) exudative (inflammatory, proteinaceous, cellular fluid): - from increased capillary and pleural membrane permeability - or pleural disease - or obstruction of flow in lymphatic channels

plexiform vascular lesion histology

vessel trying to re-canalize

asthma phenotypes

T2 high (T2 cytokines = IL-4, IL-5, IL-13) - most patients - subtypes: allergic asthma, late-onset eosinophilic, and exercise-induced asthma T2 low - poorly understood - fewer patients - subtypes: neutrophilic

histology ID image

a - intraluminal mucus b - mucous cell hyperplasia c - thickened basement membrane d - smooth muscle thickening ? - inflammatory cells

histology ID CF slide

a - mucopurulent debris b - inflamed submucosa c - ciliated respiratory epithelium

bleb

air between lung and visceral pleura

of anti-IgE, anti-IL-5, anti-IL-8, and anti-IL-17, which would be the best monoclonal antibody to impact greatest # of pts?

anti-IL-5 since it would treat both allergic eosinophilic asthma pts and non-allergic eosinophilic asthma pts *anti-IgE would only help allergic eosinophilic asthma * anti-IL-8 and anti-IL-17 would treat neutrophilic asthma

ARDS from indirect lung injury

causes: sepsis, multiple trauma, shock

asthma induced sputum samples

charcot-leyden crystals: derived from eosinophils Curschmann's spirals: from strands of mucus creola bodies: aggregates of sloughed epithelia

what part of the CNS contains the central pattern generator for breathing?

brainstem

ARDS from direct lung injury

causes: pneumonia, aspiration, pulmonary contusion, fat emboli, inhalation injury, near drowning -

mechanisms of physiologic obstruction

filling lumen with mucus in chronic bronchitis - FEV1 is reduced - FVC is normal or close to normal because pt can eventually get it out; just takes longer wall thickening/airway fibrosis in chronic bronchitis - FEV1 is reduced - FVC is normal or close to normal because pt can eventually get it out; just takes longer loss of tethering in emphysema - loss of elastic recoil - airway collapse

ILD unknown etiology diseases

includes: - sarcoidosis - CT disease-related - pulmonary langerhans cell histiocytosis - idiopathic interstitial pneumonias - diffuse alveolar himorrhage - cryptogenic organizing pneumonia - eosinophilic pneumonia

ILD known etiology diseases

inhaled dusts - asbestos (construction, ship building) - silica (mining, ceramics, quarry working) - coal inhaled organic antigens - hypersensitivity pneumonitis iatrogenic - radiation - drugs (bleomycin, busulfan, amiodarone, methotrexate)

stepwise approach for treating asthma

intermittent asthma 1: SABA prn persistent asthma - (keep emergency SABA inhaler too) 2: low-dose inhaled steroid 3: low-dose inhaled steroid + LABA 4: medium-dose inhaled steroid + LABA 5: high-dose inhaled steroid + LABA 6: high-dose inhaled steroid + LABA + oral steroid

histologic changes in muscular artery in pulmonary HTN

medial hypertrophy -> intimal proliferation -> intimal fibrosis -> plexiform vascular lesions

bronchiectasis explanted lung histology

mucus, bacterial colonies filling airways

RDS histology, high power

note collapsed alveoli (all the endothelial nuclei making up most of the image)

COP/BOOP histology

note that it is within the airspace, not in interstitium

sarcoidosis histology

note the expansion of bronchovascular stroma that pushes the vessel way out from the bronchiole

bullae

permanent air-filled space in lung parenchyma

effectors of breathing

phrenic motor neurons: in C2-C5. project to diaphragm thoracic motor neurons: in T1-T12, project to intercostals lumbar motor neurons: project to abdominals

standard of care for tobacco cessation

physiological: treat addiction to nicotine with cessation medications behavioral: treat the routine of using tobacco with behavior change counseling - 70% of patients want to stop smoking, <50% report being advised to quit, 25% receive the standard of care treatment - 10% quit with simple advice, but 28% quit if given standard of care treatment, 3-8% quit with nothing

acute DAD histology

proteinaceous fluid as leaked into airspaces -> fibrinous clogging

pulmonary sensors of breathing

pulmonary stretch receptors: - in airway smooth muscle - sense airway size and prevent over-inflation of lung (Hering-Breuer reflex) - large inflation -> apnea and expiration-lock - send afferent signals via vagus (**if vagus is cut, tidal volume will increase since you severed afferent input from the stretch receptors!) - are slowly-adapting receptors; maintain firing rate for the entire length of the stimulus pulmonary irritant receptors: - nerve endings between airway epithelia - stimulated by noxious gases, smoke, dust, cold air - afferent innervation via myelinated vagus fibers - activation increases ventilation, bronchoconstriction, coughing to eliminate stimulus - histamine stimulation in asthma - rapidly-adapting; don't maintain firing rate for the length of the stimulus juxta-capillary (J) receptors: - in external wall of pulmonary capillaries - rapidly respond to blood-borne substances, pulmonary vascular congestion, edema - afferent innervation via non-myelinated and myelinated vagus fibers - activation -> transient apnea, rapid shallow breathing, bronchoconstriction, mucus secretion - involved in dyspnea associated with left HF and interstitial lung disease