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Exam 2 Study Guide 2018

Viruses and smoking damage the cilia in the lower respiratory system that normally provide defense. Pneumococcal pneumonia is described in a case of a young male presenting with fever, chills, cough, and sweating. Community-acquired pneumonia is most commonly caused by Streptococcus pneumoniae. Healthcare-associated pneumonia patients usually have comorbidities and worse bugs require broader-spectrum antibiotics with de-escalation based on new clinical data. Hospital-acquired pneumonia occurs more than 48 hours after admission and mechanical ventilation increases the risk over 6-21 times.

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0% found this document useful (0 votes)
174 views21 pages

Exam 2 Study Guide 2018

Viruses and smoking damage the cilia in the lower respiratory system that normally provide defense. Pneumococcal pneumonia is described in a case of a young male presenting with fever, chills, cough, and sweating. Community-acquired pneumonia is most commonly caused by Streptococcus pneumoniae. Healthcare-associated pneumonia patients usually have comorbidities and worse bugs require broader-spectrum antibiotics with de-escalation based on new clinical data. Hospital-acquired pneumonia occurs more than 48 hours after admission and mechanical ventilation increases the risk over 6-21 times.

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Evan
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Lecture 14: Community Acquired Pneumonias – Bacterial and Atypical (WILLIAMS)

Viruses and smoking are good at killing cilia that normally defenses lower respiratory system
Almost no normal flora in lower respiratory system

Pneumococcal Pneumonia
Case 1: 22-year-old male awakes at 3:00 AM with fever, bed shaking chills (rigors), cough, and sweating. PMH: No ongoing medical problems. Allergies: none. FH.
Father died 50’s melanoma. SH: Nonsmoker. Occasional alcohol. Recent travel: snorkeling in mountain stream 2 days ago. HEENT: mild allergic changes in nasal mucosa.
CV RRR, no murmur. Lungs minimal rales lateral LL lung fields Dx: pneumococcal pneumonia – “see gram + stuff in sheets everywhere”
Pathogenesis
 Inhalation (Mycobacterium tuberculosis, Legionella), aspiration (#1 cause, mostly at night), hematogenous seeding (endocarditis/septic thrombophlebitis)
 Contiguous spread, reactivation (ex. P. jiroveci, M. tuberculosis, CMV) can occur in setting of deficits of cell-mediated immunity  can remain laten for many
years
Community-Acquired Pneumonia (CAP)
Case 2: 62 y/o F with mental confusion, 101.3, RR 20, BUN 31, WBC
 Pathogens: #1 is Strep pneumo M. catarrhalis common in kids and adults w/ chronic lung disease, more common in URI
 CXR is cornerstone of dx, but if negative and presents like PNA  get CT
 Pneumonia severity index (PSI)
Patient, Setting Common Pathogens Empirical Therapy
Outpatients
<60 yr Streptococcus pneumoniae Macrolide or doxycycline
No comorbid diseases Mycoplasma pneumoniae
Chlamydia pneumoniae
Haemophilus influenzae
Viruses
>65 yr or with comorbid disease or antibiotic therapy within S. pneumoniae (drug-resistant) Macrolide or doxycycline
last 3 mo M. pneumoniae fluoroquinolone*
C. pneumoniae Beta-lactam and macrolide
H. influenzae
Viruses
Gram-negative bacilli†
S. aureus †
Inpatients
Not severely ill S. pneumoniae Macrolide and cefotaxime or ceftriaxone, or beta-lactam or
H. influenzae beta-lactamase inhibitor; fluoroquinolone‡ alone
Polymicrobial
Anaerobes
S. aureus
C. pneumoniae Viruses
Severely ill S. pneumoniae § Azithromycin, or fluoroquinolone‡ and cefotaxime,
Legionella spp. ceftriaxone, or beta-lactam or beta-lactamase inhibitor
Gram-negative bacilli If P. aeruginosa possible—IV macrolide or fluoroquinolone
M. pneumoniae and aminoglycoside IV, or antipseudomonal quinolone and
Viruses antipseudomonal beta-lactam
S. aureus If MRSA possible, add vancomycin or linezolid

Initial Management – when community-acquired pneumonia suspected, determine if pt requires hospital admission using PSI
Point of Care Guidelines
 Procalcitonin Test Results:
o <0.1 ng/mL – abx strongly discouraged 0.1-0.24 ng/mL – abx discouraged
o 0.25-0.50 ng/ml – abx encouraged >0.5 ng/ml – abx strongly encouraged
o If bacterial infxn unlikely, recommend rest/cough suppressants and f/u in 3 days but NO ABX
Mycoplasma Pneumoniae - “Walking PNA”
 Common with increasing age, MOST COMMON assoc w atypical pneumonia, transmission person-person but infection spreads slowly
 Dx: Can test with rapid assay in office, hi-res CT more sensitive than CXR, CXR findings vary (junk everywhere), elevated ESR, WBC & sputum stain not
helpful (bc no cell wall), serum cold agglutinins (chill blood  sand)
 Sx: Dry, paroxysmal cough worse at night Self-limited clinical course Complications: effusion, empyema, pneumothorax, RSD
Chlamydia Pneumoniae
 Humans only reservoir, persistent latent infxn, intracellular obligate organism = CAN’T SEE IN SPUTUM, can be really bad in neonates
 Sxs  Sore throat, HA, cough x months, scant/non-existent sputum, low grade fever
 Dx: CXR  Less invasive infiltrates than other causes Usually mild, death a/w comorbidity
Legionella Pneumophila
 Intracellular, most pathogenic, Serotype 1, found in moist soil/man-made systems for heating/cooling water
 RF: overnight stays outside the home, recent home plumbing work, renal/liver failure, DM, malignancy, immunocompromised
 “If ya got a hot tub, for God sakes, put something in there to kill the Legionella”
B. pertussis
 Rare, very infectious Cough cough cough VOMIT cough cough cough VOMIT

RFs: Age, COPD, comorbidity, alcoholism ("when you're drunk, you aspirate”), cancer, neuro dz, smoking, painters, soldiers, South African gold miners
Clinical Manifestations: cough, fever, chest pain, tachypnea, sputum production *may also have confusion, HA, myalgia, abd pain, n/v, diarrhea
DX of PNA  consolidation, dullness to percussion, crackles, increased tactile fremitus, bronchial breathing, CXR not most sensitive  CT
Prevention  reduce RF (smoking, etoh), vaccination, influenza vaccine (65+ yo, chronic dz, med employees), pneumococcal vaccine (65+ yo or younger ppl w/
CV/pulm disease, DM, alcoholism, cirrhosis, etc.)

Staph aureus CAP


 Median age of 16 yo, otherwise young and healthy; 50% die in 4 days; Caused by MRSA occurring with/after influenza
 Go to the ER  call the ER and tell them you have a pt coming who had flu and now has sudden cough, SOB, new fever

Complications:
 Pleural effusion  occurs when fluid collects b/w parietal and visceral pleura
o HF or nephrotic syndrome, cirrhosis, ascites transudative Localized inflammation/malignancy  exudative
o Get a CXR (lateral decubitus to lay it out) and thoracentesis
o Light’s Criteria: to distiniguish b/w exudative and transudative effusion
 Protein/serum protein ratio >0.5
 LDH/serum LDH ratio >0.6
 LDH >2/3 upper limits of serum normal
  EXUDATE
 Lung Abscess >2cm of necrosis with confined cavitation
 Empyema – inadequate tx of underlying infxn  bacterial invasion of pleural space w/ accum of purulent fluid in pleural space; MUST DRAIN
 Bronchiectasis – uncommon dz that results in abnormal and permanent distortion of 1+ conducting bronchi or airways 2ndry to infectious process
o Detailed by Laennec and Osler and further by Reid (“you should know these guys”)
o Chronic obstructive pulm lung disease manifested by airways that are inflamed and easily collapsible  airflow obstruction, SOB, impaired
clearance of secretions w/ disabling cough and occasional hemoptysis
o Pathophys – abnormal dilatation of proximal and med-sized bronchi caused by weakening of muscular and elastic components of bronchial walls
o Species: Klebsiella, Staph aureas, TB, Mycoplasma pneumoniae, Non-TB mycobacteria, some viruses

Lecture 15: Nosocomial Pneumonias: HAP, VCAP, VAP (Williams)


Healthcare-Associated Pneumonia (HCAP)
 Def: Pma at any time in their hospital stay (on admission or acquired in the hospital), who have hx of recent hospitalization w/in 90 days, residence in nursing
home, tx w/ chronic hemodialysis, receipt of home wound care, exposure to family member w/ drug-resistant infxn
 Big thing: bugs are WORSE  inc m&m; pts usually have comorbidities (immunosuppressed, DM, chronic renal, heart dz, stroke)
 To minimize risk: early BROAD-SPECTRUM abx  de-escalation to fewer and narrower drugs w/ new clinical data (short duration)
o USE PROCALCITONIN TEST TO DECIDE WHO NEEDS ABX
Hospital Acquired PNA –
 Def: Pma that occurs >48 hrs after hospital admission, excluding any infxn at the time of admission EXCEPT if required intubation
 Epi: 2nd most common nosocomial infxn (after UTI – overrides this in ICU), high mortality rate, immunocompromised causes death
o Mech ventilation 6-21x more likely to develop (bypasses URT defenses, pools secretions, prevents cough)
 RFs: >70 yo, serious comorbidities, malnutrition, impaired consciousness, prolonged hospitalization (>5 days!)
 Pathogens
o Aerobic gram neg bacilli  Enterobacter, e. coli, klebsiella, proteus, serratia marcescens, H. influenzae
o Gram pos  strep pneumo, staph aureus
 Ventilator Associated PNA (VAP)  can be regarded as subgroup of HAP; pma occurring >48 hrs after pts have been intubated/mech vent
o Clinical Pulmonary Infection Score (CPIS) for VAP – used as adjuvant NOT major decision like PSI
o Pathogens: P. aeruginosa, Acinetobacter spp., S. maltophilia
o Dx: high clinical suspicion, CXR, micro analysis, leukocytosis (low or high!), purulent tracheobronchial secretions
o Culturing  Blind minibronchoalveolar lavage (BAL) through endotracheal tube
o Tx: local resistance patterns;
 In absence of RFs for MDR bacteria  strep pneumo, H. influenzae, methicillin-sensitive stap aureus, abx-sensitive gram-neg enteric
organisms  ceftriaxone, quinolones, ampicillin/sulbactam, ertapenem
 When RFs for MDR present, consider above + pseudomonas, klebsiella, Enterobacter, serratia, Acinetobacter, s. maltophilia, burkolderia
cepacian, MRSA  include anti-pseudomonal cephalosporin, antipseudomonal carbapenem, OR b-lactam inhibitor
 + fluroquinolone or aminoglycoside
 + linezolid or vancomycin (RED MAN SYNDROME) = MRSA
Aspiration Pneumonia
 Def: aspiration of particulate can produce acute airway obstruction and death by asphyxiation; aspiration of smaller particles may produce atelectasis of pulm
segment or even an entire lung w/ dyspnea, wheezing, and cyanosis
 CXR – RLL is most common site d/t more vertical orientation of mainstem bronchus
o Aspiration while standing  BLL infiltrates
o Left lateral decubitus  Left sided infiltrates
o RUL may be involved in alcoholics who aspirate while in prone position
 Px: mortality rate approaches 70% for massive aspiration, asp complicated by empyema 20%,
uncomplicated pneumonitis 5%
Complications of Pneumonia
 Pleural Effusion – accumulation of fluid in pleural space
o Transudate (inc hydrostatic press/dec oncotic press)  CHF and liver cirrhosis
o Exudative (capillary beds messed up)  malignant pleural disease, PE, GI disease
 Empyema – purulent fluid in pleural space
o Causes: Pma #1, lung abscess, bronchopleural fistula, esophageal perforation, post-sx complications, trauma
o Small amount of sterile fluid accumulates  higher neutrophilc counts and fibrin deposition  fibroblasts grow into pleural walls and produce
thick peel
o Sx: indicated for drainage of pus and for pts who have loculated fluid collection
 Lung abscess – parenchymal necrosis w/ confined cavitation resulting from pulm infection
 Usually tx w/ VATS (video-assisted thoracoscopic sx)
Surgical Tx of Bronchiectasis
 Children w/ recurring infection, hemoptysis, persistent chest pain, failure of medical tx
Control Measures
 Endotracheal intubation  suction secretions, extend them
 Mech vent  30-45 deg head elevation; use nonalkalinizing (tums, proton pump inhibitors)
 Don’t routinely change ventilator circuits more often that every 48 hrs; drain and discard tubing
 Condensate or use heat-moisture exchanger if indicated
 If not eating, use nasogastric tube; once better  take it out

Lectures 16 & 17: Tuberculosis and Management (M. THOMAS)


Epi:
 In US – HIV/AIDS patients, homeless, crowded housing, long-term prisoners, foreign-born immigrants, IVDU
 Worldwide – sub-saharan Africa, India, Asian/South Pacific countries
 Strong association with HIV/AIDS
RFs:
 Immunocompromised - malnutrition, substance abuse, systemic diseases, HIV, organ transplant, steroid/TNF inhibitor tx
 Exposure to infectious persons – birth in a TB-endemic country, crowded community
Micro: Mycobacterium tuberculosis (duh)
 Acid-fast, rod-shaped, non-spore former, facultative intracellular, slow growing organism
 Obligate aerobe  important because this means TB tends to grow in areas of high O2
 Grows on Lowenstein-Jensen agar
 Cell wall consisting of peptidoglycan, mycolic acids, LAM (lipoarabinomannan)
 Major virulence factor = cord factor; aka serpentine cords  plays huge role in TB survival in host phagosomes; elicits granuloma formation
 Transmission = droplets, airborne
o Droplets can remain in air for several hours  hard to get rid of TB in close contact areas
o Human host is only natural reservoir
Pathophys
 Inhaled infective droplet  well-ventilated middle and lower-lobe alveoli; ingested by macs
 MTB interferes w/ acidification of phagosome rendering lysosomal enzymes less effective  multiple in phagosome of mac
 Triggers Th1 immune response  activates macrophages
 Delayed Type Hypersensitivity Response (Type IV Hypersensitivity)
 Interferes with acidification of phagosome  leaves TB free to multiply within the nonactivated macrophages
 Grows as a caseating granuloma
 Ghon complex: when granuloma calcifies with hilar lymphadenopathy (picture)
 Miliary TB: essentially disseminated TB  death (only occurs in about 10% of active TB, the other 90% remain confined to pulm)
 Latent TB: when an individual is infected with m. tuberculosis but immune system can contain it; can progress to secondary TB,
resulting in active TB, military TB, or healing and fibrosing of the lesion
Clinical Presentation
 Early: Fever, night sweats, weight loss, malaise, weakness, blood-streaked cough that is nonproductive
 Progressive: dyspnea, rales, further wasting, anemia, leukocytosis, thrombocytosis, ^ ESR
LTBI
 Not infectious but will present with positive skin test
 10%  active TB (being HIV+ or being <5yo increases this chance)
 Usually have a normal CXR, be asymptomatic, have negative sputum smears/cultures
 Should consider treatment in order to prevent active TB dz but does not require respiratory isolation
Primary TB
 Usually in children, pts w/ impaired immunity very soon after initial infection
 Middle and lower lung zones because droplets inhaled
 Common to see pleural effusions, NEED TX, + cultures
Secondary TB (aka post-primary or reactivation or adult-type)
 Apical and posterior segments of upper lobes because higher O2
 Extent varies from small infiltrates to extensive cavitating disease (caseous necrosis)
Miliary TB
 CXR shows millet seed appearance (picture)
 Frequently fatal, can occur from either primary or secondary TB
Extrapulmonary sites:
 Lymph nodes – usually parotidal, submandibular, supravclavicular regions; can be b/l
o Firm and well-defined at first, but softens and can perforate/ulcer with progression and enlargement (ulceration)
 Pleura – effusion can occur without granuloma; can be due to hypersensitivity response to mycobacterial antigen
 GU
o Male – painful scrotal mass, prostatitis, orchitis, epididymitis
o Female – mimics pelvic inflammatory disease
 Skeletal – usually WB joints
o Pott’s disease – involves 2+ adjacent vertebral bodies (Can eventually compress spinal cord  paraplegia)
o Gibbus – when vertebral bodies collapse and result in kyphosis
 Meninges  Usually children and HIV+ patients
o Can present as HA, subtle mental changes  coma, hydrocephalus
 Peritoneum – abdominal pain, swelling, ulcerations, fistula
 Pericardium – can progress to cardiac tamponade  fatal w/o tx
 Adrenal
Hx
 Should focus on potential exposure to TB, risk factors, past TB treatment, and symptoms of TB
 Possible extrapum TB can present with: blood in urine, HA/confusion, back pain, hoarseness, loss of appetite, night sweats, fever, fatigue (really anything…)
Dx
 First step: find and test uninfected persons at high risk for LTBI and/or persons at high risk for progression to active TB
 TST or IGRA
o Done in individuals suspected to have TB but w/o sx (if pt has sx of TB, skip straight to CXR)
 PPD/TST  causes delayed-type hypersensitivity (DELAYED  Th1 cells)
o Purified protein derivative is injected between skin layers (Mantoux technique)  read 48-72 hours later
o Takes 2-8 weeks after exposure to produce positive result, so can produce a false negative if patient was very recently exposed
o Redness = doesn’t mean anything
o Induration  record in mm, means + test

 False +  non-TB mycobacteria, BCG vaccination, probs w/ TST administration


 False -  anergy, co-infection, recent TB infxn, very young/old, live vaccination, overwhelming TB dz, renal failure, low protein, admin…
 2-step test done in healthcare professionals
 Interferon-Gamma Release Assay (IGRA)
o Blood test; more specific than PPD/TST and only requires one pt visit
o Can distinguish false + d/t BCG vaccine (individual immunized with BCG will not read as positive on IGRA but will have a positive PPD)
 CXR
o 1st step performed in pt w/ TB symptoms or 2nd step performed in pt w/o sx but with a positive
TST/IGRA
o If abnormal in either group of patients  culture sputum
 Sputum culture
o Can be induced by hypertonic saline or BAL on bronchoscopy
o Gastric lavage used in children
o Ziehl-Neelsen basic fuchsin dyes used  acid-fast smear
o Should culture all specimens – this is gold standard for diagnosing
 Grows slowly, but we have faster methods now
o Nucleic acid amplification should be performed on at least one diagnostic specimen,
takes <48hrs
 After dx latent vs active tuberculosis  check HIV status (+ changes treatment)
Treating LTBI
 Isoniazid (INH) x9 months daily = gold standard
o Can alternatively be given INH twice weekly via DOT
 After LTBI tx, giving patient documentation on how they got treated, what they got treated with, etc. is important; also educate on TB symptoms in case they
progress to active
Treating active TB
 Initial = 4 drug regimen (Rifampin, Isoniazid, Pyrazinamide, Ethambutol) for 2mo (RIPE)
 Continuation = INH and RIF for 4-7mo
 Patient monitoring is very important!!!
o Directly Observed Therapy – government-funded to make sure we’re
treating TB pts adequately; has been effective in reducing TB-assoc
deaths; also involves giving incentives to TB pts to take their meds, go
to health care appts, etc.
o Lack of adherence = most important impediment to cure worldwide
 When to consider drug resistance: If cultures do not convert to negative after 3
months (or evaluate for adherence issues)
o Consider tx failed after 4 mo
Prevention:
 BCG vaccine – not widely used in US but given to infants/children in other
countries; not always effective
o Can produce false positive on PPD/TST
o Consists of live, attenuated m. bovis strain
 Respiratory isolation of active TB (N-95 mask, negative pressure room)
MDR-TB/XDR-TB
 Most common in countries with high rates of HIV (South Africa, India, Asia)
 Subtypes:
o Drug-resistant TB = isolate resistant to 1 first line drug
o MDR-TB = isolate resistant to INH and RIF
o XDR-TB = isolate resistant to INH, RIF, and fluoroquinolone + aminoglycoside or capreomycin
 Highly associated with HIV+ Prevalence in Russia, Eastern Europe, China, India
o TDR-TB = isolate resistant to all locally tested meds
 Prevalence in South Africa, India
 Higher mortality, requires more meds and longer tx, sx may be required to resect affected lung area
 Resistance can occur by: Primary – spontaneous chromosomal mutation
o Secondary (more common) – due to poor drug regimen adherence, inappropriate rx, monotherapy
 Drug susceptibility screening should be initiated at the start of tx!
 If pt failing drug regimen, check for resistance and rescreen for HIV status
 Using multiple drugs from different classes = important for combatting resistance

Lecture 17: Respiratory Failure (EKEY)


Five Causes of Hypoxemia
Cause Pa02 A-a gradient E.g. clinically

High altitude (low ambient O2) ↓ normal Mountain climbing

Hypoventilation ↓ normal Drug overdose, Guillain-Barre, chest wall prob

Diffusion defect ↓ ↑ Rare.

V/Q defect ↓ ↑ PE, pneumonia, ARDS

Right to left shunt ↓ ↑ Congenital heart disease

Respiratory Failure
 Inadequate oxygenation to meet metabolic needs and/or inadequate excretion of CO2
 Criteria: (1) PO2 < 60 mmHg, or (2) O2 sat < 93% on >60% oxygen, with (3) Rising/clinical apnea
 A problem anywhere in resp system can lead to failure  acute, chronic, acute on chronic
 How to respond to the three main causes of respiratory failure:
o Failure to ventilate (High PaCO2)  Increase minute ventilation, NIPPV, IPPV
o Failure to oxygenate (Low PaO2)  Increase FiO2, apply CPAP, Increase mean airway pressure
o Failure to protect airway (low GCS)  Becomes failure to ventilate w/ decreased Resp drive  Intubation
Failure to Ventilate (Hypercapnic Respiratory Failure)
 Failure to exchange or remove CO2
 Causes:
o Decreased respiratory drive: Sedating drugs, brain injury, severe hypothyroidism
o NM disease: SC injury, MG, ALS, steroids, flail chest, obesity
o Lung diseases: Pleural effusions, pneumothorax, COPD, asthma, etc.
 Tx: Reverse underlying cause and give positive-pressure
Failure to Oxygenate (Hypoxemic Respiratory Failure)
 Failure of O2 exchange  Decline in oxy-Hb saturation that doesn’t readily correct with supplemental O2
 Five basic causes:
o RT to LT Shunt: (1) pathologic vascular communications, (2) Space-filling pulmonary parenchymal lesions
o VQ Mismatch, Reduced diffusion capacity, Alveolar hypoventilation, Low fraction of inspired air (high altitude)
Failure to Protect Airway
 Ultimately becomes failure of ventilation  dec resp drive (sedating drugs, brain injury, severe hypothyroidism, sleep-disorders)
Management of Respiratory Failure
 ABCs: Airway protection, supplemental O2 and assisted ventilation, support circulation

Mechanical Ventilation
 Positive-Pressure: Air is forced into the central airways, into the alveoli  Lung inflation
o Exhalation reverses the pressure gradient
 Can be invasive or non-invasive; controls many factors of ventilation: FiO2 of inspired air and the RR
 Non-invasive positive-pressure ventilation (NIPPV)
o To protect airway in hemodynamically stable patient (AWAKE)  Facemask, nasal prongs
o Indications: Non-emergent need for intubation and diseases that respond to O2 (COPD, cardiogenic pulm edema)
o CIs: cardiac arrest, impaired consciousness, facial deformities, inability to cooperate
o Improves laminar airflow by stenting obstructed airways w/o mechanical assistance
o Decreases atelectatic alveoli, improving pulm compliance, and reducing work for breathing
o CPAP (1 fixed continuous pressure) or BiPAP (two pressures: Ipap and Epap) Ipap > Epap
 Invasive Mechanical Ventilation: ET Tube or Tracheostomy if upper airway obstructed
Disorders with Respiratory Failure
Obstructive Sleep Apnea “neck fat in the way”
 Repetitive narrowing/occlusion of upper airway during sleep leading to apneas and hypopneas
 Occurs during REM sleep with muscle atonia
 Pathophys: Lack of airflow for several seconds  Increased effort to breath against occlusion  Negative intrathoracic pressure
o Leads to brief awakening from sleep (Microarousal)
 Adult RFs: OBESITY, large neck, alcohol, sedatives
 PEDS RFs: Tonsillar hypertrophy, macroglossia, retrognathia, upper airway mass
 S/S: Loud snoring and gasping, frequent awakening, non-restorative sleep
 Dx: Polysomnography and overnight at-home pulse Ox
 Tx: Weight loss, CPAP, Uvuloplatopharyngoplasty, oral mandibular advancement device to protrude jaw
 Complications: HTN, PAH, CAD, arrhythmias, HF, stroke, DM
o Overall 2-3x increased risk of mortality vs those without OSA
Central Sleep Apnea *CNS injury/toxicity/HF/opiods
 Loss of ventilator output from central respiratory generator in brainstem to the respiratory pump
o Results in absence of respiratory effort with loss of airflow
 Pathophys: Hyperventilate and drive down PCO2 to a level near apneic threshold, so respiratory effort ceases
 RFs: CHF, A-Fib, CVA, Cheyne-stokes breathing
 S/S: Insomnia, excessive daytime sleepiness, paroxysmal nocturnal dyspnea
 Dx: Polysomnography Tx: Underlying disorder, reduce opioids, PAP
Obesity Hypoventilation Syndrome (Pickwickian)
 Obese patient developing awake alveolar hypoventilation which cannot be attributed to another condition
o Obesity  > 30 BMI Alveolar hypoventilation  PaCO2 > 45 mmHg
 Causes: Pulmonary HTN and RT-sided HF
 S/S: same as OSA
 Dx: High [Bicarb] and O2 sat < 93% on room air
o ABG: PCO2 >45 while awake, PaO2<70
o PFTs: Restrictive lung function possible
o EKG/Echo: right atrial and right ventricular hypertrophy
 Tx: Nocturnal noninvasive positive airway pressure & wt loss
Hypercapnic Respiratory Failure
 PCO2 > 50 mmHg; hypoxemia on room air common
 The pH depends on level of bicarb, which is dependent on duration of hypercapnia
 Causes: Drug OD, NM diseases, chest wall abnormalities, asthma, COPD
 Acute Respiratory Acidosis: develops over minutes to hours
o Kidneys don’t have time to compensate, so the pH drops below 7.3
o Example ABG: pH 7.16, pCO2 70, HCO3- 27, pO2 88
 Chronic Respiratory Acidosis: develops over several days
o Kidneys can compensate by increasing bicarb, resulting in pH remaining above 7.3
o Example ABG: pH 7.31, pCO2 70, HCO3- 36, pO2 88
Acute Respiratory Distress Syndrome (ARDS)
 Alveolar injury d/t acute, persistent, diffuse lung inflammation, resulting in non-cardiogenic pulmonary edema
 Etio: most commonly caused by sepsis
 Pathophys: Alveolar injury  Release of TNF-a, IL-1, IL-6, IL-8  Neutrophil recruitment to lungs
o Neutrophils release toxic mediators (ROS, proteases), damaging capillary endothelium and alveolar epithelium
o Increased vascular permeability allows leakage of proteins, fluid, and neutrophils into the alveoli
o Air spaces fill with bloody, proteinaceous edema
o Functional surfactant is lost, causing lung collapse (atelectasis)
o Results in increased work for breathing, impaired gas exchange, and decreased pulmonary compliance
 Ssx: Rapid onset of severe dyspnea, hypoxemia, and respiratory distress (tachypnea, diaphoresis)  respiratory failure
o Hypoxemia with respiratory alkalosis and elevated A-a gradient
 Criteria for Dx:
o Acute onset within 1 week of an apparent clinical insult or development and progression of respiratory symptoms
o Bilateral opacities on chest imaging not explained by other pulmonary pathology
o Respiratory failure not explained by heart failure or volume overload
 Tx: High [supplemental O2] needed, intubate and mechanically ventilate; fluid management & adjuncts
o Use of lower tidal volumes may reduce lung stretch and lead to better outcomes 6 mL/kg TV’s (ARDSNet TRIAL) = Gold standard
o Ventilator-free days improved, decreased circulatory, coagulation and renal failure
 CXR resembles pulm edema/hemorrhage  Diffuse B/L opacities CT: parenchymal consolidation in the gravity-dependent areas of the lung
Acute Inhalation Injuries
 Inhalation is most common exposure route & most common cause of fatalities related to toxic exposures
 Toxin is absorbed and causes systemic toxicity and/or directly injures pulmonary epithelium at several levels of RT
 S/S: Related to hypoxia
o Indifferent Stage (mild): Decreased night vision, tachycardia
o Compensatory stage (Sats in 80s): HA, tachypnea, tachycardia, angina, air hunger
o Disturbance stage (Sats in 70s): Decreased vision, impaired coordination & judgement, extremity numbness
 Physical Exam  Tachypnea, tachycardia, cyanosis, abnormal cerebellar findings
o Critical Stage (Sats <64): Rapid deterioration of coordination and judgement, LOC w/in mins, and seizures
 Simple Asphyxiants act by displacing O2 from inspired air and lowering FiO2
o Tx: Removal from exposure and supplemental O2

 Chemical Asphyxiants act by interfering with O2 delivery or O2 utilization

Irritant Inhalation
 Chlorine, ammonia, sulfer dioxide, phosgene
 S/S depend on solubility and particle size of the irritant
o High solubility: deposit in nose, URT, and large airways; low solubility: deposit in small airways and alveoli
 Dx: ABG (hypoxia, inc A-a gradient), CXR (pulm edema, atelectasis, infiltrates), EKG, and Carboxy-Hb level Tx: supportive
Smoke Inhalation Injury
 Dx: Hx of exposure to fire in an enclosed space
 PE: Burns, singed nasal nares, soot around nares, carbonaceous sputum, hoarseness, stridor, respiratory distress, expiratory wheezing, and carboxy-Hb > 10%
o Even if they are up and talking to you, but have these PE findings, jump on them and intubate EARLY! They will go downhill fast and start swelling
 Tx: Humidified O2 (100%) by mask, ABG (carboxyhemoglobin levels), control upper airway by ET intubation
Anaphylaxis
 Type 1 IgE-mediated allergic hypersensitivity reaction with rapid onset, can cause death
 D/t overreaction of immune system to antigen, causing degranulation of mast cells and basophils
 Histamine targets H1 and H2
o H1 causes tachycardia, pruritis, rhinorrhea, and bronchospasms
o H1 and H2 mediate flushing, hypoTN, and HA
 Tryptase of mast cells activates complement and coagulation pathways, and the Kallikrein-Kinin contact system
o Causes hypoTN, angioedema, clotting, and clot lysis
 Allergen stimulates Th2 cells and IgE production  IgE binds Fc Receptor on Mast cells  Repeat exposure activates mast cells to secrete mediators  Type I
Hypersensitivity reaction (Clinical Dx)
 Initial Treatment: IM EPI (DO NOT WAIT), repeated 1 5 – 15 min with adjuvant
H1 and H2 blocker, and glucocorticoid Consequences of COPD

Lecture 19: COPD “The Basics” (GEORGES)


COPD-slowly progressive inflammatory disease of airways and lung parenchyma w/ gradual
loss of lung function and increasing obstruction to expiratory airflow.
 Largely irreversible
 Chronic Bronchitis and Emphysema are outdated terms that we will still use and
be tested on (surprise!)
 RFs-usual stuff (tobacco, exposure to small particles etc),“indoor air pollution
from heating and cooking biomass in poorly ventilated dwellings.”
o Women < 65 in all races more than men; previous TB, socioeconomic status
 Suggestive Features of COPD
o Onset in mid-life, sx slowly progressive, long hx of smoking, dyspnea w/ exercise, largely irreversible airflow limitation.
Emphysema-an anatomical diagnosis
 Permenent enlargement of airspaces (acini) distal to the terminal bronchioles
 Respiratory bronchiolecerilobular(centrilacinar)smokersupper lung zones (SMOKE RISES ^)
 Entire airspacepanlobular (panacinar)A1 antitrypsin deficiencylower lung zones
 Pathophys: can have any or all of the following processes  disrupted alveolar attachments, mucosal and peribronchial inflammation and fibrosis, and
mucous hyper secretion.
 Pink Puffer
o Thin, muscle wasting, often use pursed lip breathing (auto peeping)
o Often use accessory muscles and are anxious (tripod)
o Increased AP chest diameter (barrel chest)
o Flat, immobile diaphragms, distant BS, hyper resonance to percussion on exam
o Small heart on chest x-ray, low BP
o ABGs are normal unless end stage or infection (PaO2 of 65, PaCO2 of 37, pH 7.39, HCO3-26, Sat 92%), low DLCO (alveolar units are destroyed)
Chronic Bronchitis-blue bloater
 Cough w/ sputum >3 mos for 2 or more years
 Plethoric and cyanotic appearing with an elevated H and H
 Obese, peripheral edema, JVD, Cor Pulmonale
 A lot of bronchopulmonary secretionscoarse breath sounds
 Centrilobular pattern w/ hyperplasia of mucous glands in bronchi and bronchioles.
 Chest x-ray “DIRTY”  normal diaphragm w/ a lot of congestion. Looks like CHF
 “Hallmark is cough” with marked sputum production
 50/50 club: They are chronic CO2 retainers. PaO2 of 50 and PaCO2 of 60.
 Reid Index- will be above 0.4 (normal)
o Thickness of mucous gland layer to thickness of wall btw epithelium and cartilage (bc/ad)

Other COPD Diseases


 A-1-Antitrypsin Deficiency-Protein made in the liver that prevents enzymes (trypsin, chymotrypsin, and neutrophil elastase) from breaking down the elastin in
lung
o Panacinar emphysema in youngins (<50)
o PiMM normal; PiZZ severe emphysema
o “The pattern of basilar emphysema, liver disease, and family history of emphysema in patients with COPD should prompt consideration of α1-
antitrypsin deficiency in middle age and older patients.”
 Bronchiolitis Obiliterans-from inhaling toxic fumes, viral infections, connective tissue disorders, transplant.
o Dx w/ CT or lung biopsy. Classic obstructive pattern
 Rx w/ macrolide abx and immunosuppresives
 Allergic Bronchopulmonary Aspergillosis – asthma, eosinophilia, inc IgE, transient/fixed pulm infiltrates (love to ask about this on boards)
o Rx-steroids
 Lymphangioleiomyomatosis – rare, cystic lung dz w/ proliferation of lymphatic tissue
o Affects only fertile women?
o Assoc. w/ tuberous sclerosis gene complex
o Interstitial changes, repeated hemoptysis, “swiss cheese” on chest CT
o Rx-sorolumus (rapamycin) or lung tx
o PNEUMOTHORAXI
 Bronchiectasis-irreversible dilation and destruction of one or more medium sized bronchi w/ inadequate clearance and pooling of mucous in the airways.
(smells like decomp flesh)
o Cylindrical, varicose, cystic, follicular, and traction
o Chronic inflamm, repeated infx, obstructive and restrictive defects
o Multiple predisposing factors
o Signet Ring Sign on CT
o Multifaceted Tx.
Diagnosis and management of COPD
 Consider it in any pt w/ dyspnea, chronic cough, intermittent wheezing, sputum production, dec exercise tolerance, hx of significant exposure to tobacco
 Spirometery is essential for dx-pre and post inhaled bronchodilator
o Don’t screen asymptomatic pts
o Post Bronchodilator FEV1/FVC ratio of less than 70%
 Severity defined based upon a ton of stuff, but the main ones we MUST know are the GOLD Criteria
Goals of Tx
 Bronchodilation
 Decrease airway inflammation
 Improve mucocilliary clearance
 Aggressively treat all acute exacerbations of COPD
 Chronic O2 Therapy
Tx Suggestions
 Avoid airway irritants, stop smoking, bronchodilators and anticholinergics, steroids, oral, IV, and/or inhaled, vaccinations with Pneumococcal and influenza
vaccines, oxygen both in the acute and chronic setting, antibiotics for acute exacerbations
Pharm Therapy
 Pharm-doesn’t decrease progressive decline in lung fx, just reduces sx and freq of exacerbations
 Mainstay of tx  symptomatic and mild dz (FEV1-60%-80%) B2 agonist +/- anticholinergics
o Advocated for all levels of COPD for “breakthrough” sx.
 FEV1<60%  Inhaled long acting B-2 agonist or anticholinergic monotherapy on a daily maintenance rx
o If pt remains symptomatic then combo therapy advocated
 Advanced poorly controlled disease=triple therapy  B2 agonist, Inhaled anticholinergic, inhaled corticosteroid
 ALWAYS HAVE BETA-2 INHALER
 Steroids  never used as monotherapy/primary therapy
o Oral steroids are short term use only for acute exacerbations
o IV for hospitalizations
 PDE4 inhibitors  NOT FOR EMPHYSEMA-only Chronic Bronchitis
 Don’t use mucolytics or antitussives
 DO use Narcotics for advanced COPD to treat SEVERE dyspnea
 Abx  YES for infectious exacerbations
o Flouroquinolones, 3rd gen cephalosporin +macrolide (even if viral exacerbation)
 Oxygen Rx  indicated for severe COPD and resting hypoxemia
o PaO2 <55 or Sat <88% on RA
o Decreases at night or w/ exercisecor pulmonale
 Vaccines  pna and influenza-can give both even if < 65
Refer to Pulmonologist if:
 Rapidly progressive course
 Optimal Rx but COPD severe
 Diagnostic uncertainty
 Onset of comorbid conditions
 Need for 02 Rx
 Symptoms disproportionate to the severity of airway obstruction
 Suspect α1 antitrypsin def.
 Possibility for lung transplant or resection Rx, pre-op eval. other
surgery
 Frequent exacerbations and persistent symptoms despite adequate
Rx
 Need 2nd opinion
 Disease onset before age 40
Other Therapy
 Stop Smoking
 Pulm Rehab-Absolute necessity for all pts w/ FEV1<50%
o Results in overall improvement in quality of life, decrease dyspnea and fatigue
 Lung Volume Reduction Therapy – remove up to 30% of disease/non-functioning lung parynchmya
o Increases elastic recoil pressure of lungs
o Indications-KNOW THESE
 Advanced COPD w/ FEV1<45% but >20%, DLCO>20%, maximized pharm therapy and still sx, and primarily bilateral upper lobe
emphysema
 Improves quality of life but not survival
 Lung Transplant – improves quality of life and functional capacity but doesn’t improve survival
o Primary cause of mortality  bronchiolitis obliterans
o Indications – FEV1<20%, PaO2<55-60, PaCO2 >50, and 2nd pulmonary HTN
o Contraindications – continued smoking, substance abuse (current/w/in last 6 mos) CA w/in 2yrs, untreated advanced dysfunction of another organ
system, noncurable extrapulmonary infx, chest wall/spinal deformity, can’t comply w/ medical rx, untreated psych issues, and no reliable social
support

Lecture 20: Acute COPD Exacerbation Management (Georges)


Acute Exacerbation of COPD: worsening of the pt’s resp sxs that is beyond normal day-to-day variations and leads to a change in the pt’s med
 Winnipeg Criteria: worsening dyspnea, increasing sputum volume, purulent sputum
 Risk for Exacerbations:
o 2+ exacerbations in past yr greatest predictor of future
exacerbation
o Baseline FEV1<50% predicted
o Hx of GERD, underlying comorbidities of CAD, CHF, other
comorbidities
 Signs of Severity
o Acidosis + significant comorbidities +vents
o Other predictors-old, low BMI, poor quality of life/functional status
before admission, Cor Pulmonale, Hx of CHF, low serum albumin
(liver failure)
 Management of Acute Exacerbation
o Remember ABCS, IV, O2, Monitor
o Want to maintain a sat >90% w/O2
o Usual PE, CXR, ECG, labs to include ABGs (for A-a gradient)
o Intermittent or continuous nebs of short acting B2 &
anticholinergics, NO theophylline
o Fluouroquinolones or 3rd gen cephalosporin +macrolide
o Steroids  IV or PO-prednisone 40mg/day for 5 days
o Reassess constantly, admit or discharge
 Pts who need admission: Underlying severe COPD, advanced age, marked increase in intensity of sx, significant comorbidities, new arrhythmias, diagnostic
uncertainty, insufficient home support, onset of new physical signs, failure to respond to initial out-pt tx.
 Indications for Immediate Admission to ICU
o Severe dyspnea responding inadequately to emergency tx, AMS
o Persistent/worsening hypoxemia, severe/worsening hypercapnia or resp acidosis
o Hemodynamic instability
O2 Therapy   
 Humidified High Flow Nasal O2
o Creates PEEP in the airway – keeps alveoli expanded  improves PaO2
o What he failed to say is that you want to avoid intubation at all costs, COPDers don’t
do well on vents bc they become dependent (never come off and require a trach, or
spend a long time on the vent…get VAPs etc)
Criteria for Noninvasive Positive Pressure Ventilation
 Inclusion Criteria (2 of the following): dyspnea w/ use of accessory mm of ventilation, paradoxical chest wall motion, RR > 25, pH 7.30-7.35; PaCO2 45-60
 Exclusion Criteria (1 of the following): AMS, resp arrest, high aspiration risk, CV instability, recent facial of GI sx, extreme obesity, nasopharyngeal
abnormalities
Noninvasive + Pressure Ventilation (BI-PAP)
 The reason you intubate COPD pts is bc they get tired so don’t delay NPPV.
 Start with an IPAP of 8-12 and EPAP of 3-5. You want a difference between IPAP and EPAP ~5mmHg. If they’re the same then you have CPAP (not bipap).
 ABGs in 20-30mins  improving = good; worse = intubate and throw on ventilator
 Benefits: dec work of breathing, inc O2 and CO2 exchange at alveolar and tissue levels, improved preload/afterload of LV  inc CO, reduced need for
intubation, reduced ICU length of stay, reduced hospital cost, reduced mortality?
Indications for Intubation w/ Mechanical Ventilation

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o
 Initial Ventilator recommendations: Initial TV 6-8cc/kg, low PEEP (2.5-5.9 cm H2O), assist control mode, RR 10-12, prolonged expiration time (I:E ratio 1:3-4)
Discharge Criteria
 Pt improved and manifest stable vital signs and stable ABG’s for the past 12-24 hrs
 No longer requires short acting B-2 agonist therapy more often than every 4 hrs
 Pt and his support (family, friends, etc.) understand the correct dosages and usage of medications.
 F/u visit has been scheduled with primary care physician in 2-4 weeks after hospital discharge or sooner if indicated.
 If pt required 02 in hospital and still needs 02 at d/c then f/u in 2 wks or less with reassessment of 02 level on ambient air is indicated. (first xray is CHF from
acute MI, 2nd is chronic bronchitis)

Review of Blood Gases and Compensation


 Respiratory Acidosis
o Acute: for every ^ by 10 in PCO2, pH decreases by 0.08; HCO3- increases by 1 mEq/l *assume 7.40 pH to start if not given
o Chronic: for every ^ by 10 in PCO2, pH decrease by 0.03; HCO3- increases by 4 (kidney has kicked in)
 Respiratory Alkalosis
o Acute: for every ^ by 10 in PCO2, pH increases by 0.08; HCO3- decreases by 2 mEq/l
o Chronic: for every ^ by 10 in PCO2, pH increases by 0.03; HCO3- decreases by 5
 ACUTE COMPENSATION = LUNGS CHRONIC COMPENSATION = KIDNEYS

Lecture 21: Influenza & Other Respiratory Tract Infections (M. THOMAS)
Pathophysiology
 Resp dz is 75% of all acute morbidity in USA lowest in summer & highest in winter
 Resp viruses alter bac colonization patterns, ^ bac adhesion to resp epi, reduce mucociliary clearance & phag  allows 2ndry bac infxns
Common Cold
 Most common acute illness in industrialized world low grade fever w/ Eustachian tube dysfunction
 Rhinovirus is prototype for this clinical syndrome Tx: sx (NSAID, nasal spray, cough syrup, decong); OTC not approved for kids <6
 OTC cough and cold medicine not approved if <6 y/o b/c efficacy isn’t there and increase risk of toxicity
Alternative therapies for common cold Tx
 Zinc –reduce severity & duration of cold, can lead to permanent anosmia intranasally
 Vitamin C – no reduction when sx
 Echinacea – failed to demonstrate a beneficial benefit
 Nasal saline – no improvement in nasal sx or illness duration but did improve mucociliary clearance
Pharyngitis = sore throat
 Sx: sore throat when swallowing, “swollen glands” on ant neck, nasal congest, hoarseness, tender, ear pain
 PE: pharyngeal erythema, tonsillar hypertrophy & purulent exudate, palatal petechiae
 Tx: NSAIDS/Acetaminophen, steroids used for VERY severe cases (if pt has undiagnosed cancer – you can partially tx it and make them high risk)
 Exudative: virus (coxsackie A, HSV, EBV) or bacteria (GAS, anaerobic, C. diptheriae = GRAY) – is there pus or nah?
 Non-exudative: adenovirus, influenza, rhinovirus, coronavirus (posterior nasal drainage)
Acute Bronchitis
 Severe & prolonged cough that continues after other sx of acute infection have subsided
o Sputum, fatigue, chest discomfort, sore throat, myalgia, NO FEVER (if there is a Fever think…  flu or PNA)
 Causes: ALL VIRUS (adenovirus, rhinovirus, coronavirus etc)
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 Why do we cough? Direct damage to res mucosa, release of inflame substances, ^ produce/decrease clear secretions, stimulation of airway irritant receptors
 Tx: sx; honey as efficacious dextromethorphan & cough suppressants (no honey to <1 y/o b/c botulism) (NO ABX)
o No evidence to support using OTC meds
Reye’s Syndrome
 No aspirin to kids w/ viral illness Acute noninflam encephalopathy & fatty degenerative liver fail
Influenza like illness
 Rapid onset (“ton of bricks”) constitutional sx – fever, chills, fatigue, HA, resp sx but systemic sx appear first then respiratory sx predominate
 Cause: influenza, adenovirus, parainfluenza, RSV Dx: clinical Tx: supportively
Flu vs cold
 Flu: sudden onset, high fever, severe fatigue, severe cough, sore throat, achy muscles/head, decrease appetite
 Cold: gradual onset, low fever
Viral Pneumonia
 Worse in extreme ages, influenza responsible >50% (also RSV adenovirus, parainfluenza)
 Present: overlaps w/ bacterial pneumonia & distinction on clinical hx alone is not always possible
o Story = “Getting better and then got terribly worse”  think secondary bacterial Infxn
Microbiology by age for pneumonia
 Children (4w-18y) – RSV, Mycoplasma, Chlamydia trachomatis, C. pneumoniae, S. pneumoniae
 Adults (18-40) – Mycoplasma, C. pneumoniae, S. pneumoniae
 Adults (40-64) – S. pneumoniae, H. influenza, anaerobes, viruses, Mycoplasma
 Elderly – S. pneumoniae, influenza, anaerobes, H. influenza, gram neg rods
Orthomyxoviridae- ssRNA
 Enveloped glycoproteins have hemagglutinins (HA) & neuraminidase (NA)
o 3 types: Influenza A, B & C (B has more GI Sx)
 Transmission: virus containing resp secretions Epidemics: winter months
Influenza
 High frequency of antigenic variation  drift (small antigenic changes) & shift (large change w/ replacement of HA or NA w/ novel)
 Clinical: fever, chills, HA, myalgia, malaise, non-productive cough, sore throat, nasal discharge *Rales, rhonci, wheezes, prolonged exp phase
 Incubation: 1-5 days Dx: immunologic detection of antigens via sample
 Tx: supportive care or antiviral if early  Neuraminidase inhibitors (Oseltamivir, zanamivir, peramivir) = reduce duration of illness if initiated <48 hrs after sx
 Complications: myocarditis, pericarditis, rhabdo, Guillain-Barre (can get from vaccine or flu so might as well get the vaccine)
 High Risk for complications: <5 y/o or >50 y/o, pregnancy, chronic disease, immunosuppressed, nursing homes, Native Americans/Alaskans, obese
 Can cause secondary bacterial pneumonia about 5-10 after onset (strep pneum, staph aureus, H. flu)
 Flu Vaccines: standard-dose tri & quadrivalent inactivated (IM, intradermal, jet injector), high-dose trivalent inactivated (>65 yo), quadrivalent inactivated
produced in cultured cells (uses mammalian cells vs hens’ eggs), trivalent inactivated produced using recombinant DNA (severe egg allergy)
o Everyone 6 months and older should get a flu shot  best prevention
o NO YOU CAN’T GET FLU FROM VACCINE
Adenovirus – dsDNA
 Non enveloped linear dsDNA, close groups such as military recruits, hospital wards, psych units, dorms
 Clinical: conjunctivitis, rhinitis, fever, chills, myalgia, fatigue, bronchitis, pharyngitis
o Can be fatal w/ necrotizing bronchiolitis
 Dx: clinical, PCR, immunoassay, Ab assays Tx: sx/supportive (self-limited) Prevention: vaccine in military
PaRaMyxoviridae – (Parainfluenza – croup, RSV – bronchiolitis in babies, Rx- ribavirin, Measles & Mumps) – KNOW THE FAMILIES THEY BELONG TO
 Human metapneumovirus – neg ssRNA that causes upper/lower resp tract infections; closely resembles RSV
 Parainfluenza – ssRNA, common virus that infects most ppl during childhood, cause croup & bronchiolitis
 RSV – ssRNA, infects very young & very old, most common ause of LRTI in kids <1 y/o
o Transmission: fomites & aerosols Dx: rapid antigen test Tx: supportive care, Prevention  Synagis for Premies (passive Ab’s)

Picornavirdidae –
 Rhinovirus – ssRNA, early fall & late spring, in school kids, indistinguishable from other resp viruses
o Half of all viruses recovered from middle ear effusions w/ AOM
o Dx: PCR rapid dx, culture from NP wash Tx: supportive
Herpesviridae – HSV, VZV, CMB, EBV
 Immunocompromised: CMV, HSV, VZV
 CMV – linear dsDNA, eosionophillic intranuclear inclusions (owl eyes), down regulation of HLA
o TORCH infection Immunocompromised Tx: ganciclovir & IG
Zoonotic – Hantavirus, SARS, MERS
 Bunyaviridae  Hantavirus – inhalation of rodent urine, cause hantavirus pulm syndrome (fever, myalgias, non-CARDIOGENIC SHOCK w/in 48 hr of admit)
o Bunyaviridae infects the pulm capi endothelium after inhalation Dx: ELISA Tx: none for HPS, mech vent
 Coronaviridae
o Coronavirus – ss + sense RNA, typical coryzal illness (common cold, AOM, asthma, pma, bronchitis; winter/spring)
o SARS – originated in bats, jumped to civets & then to humans, transmission via fomites
 Diffuse alveolar damage, Type 2 pneumocyte hyperplasia, squamous metaplasia, damage to pulm epi
o MERS (middle east) – camels are intermediate host
 Sx: fever, chills, cough, SOB, pneumonia, ADS, GI sx

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Lecture 22: Fungal and Opportunistic Respiratory Infections (M. THOMAS)
Fungal pneumonias
 Caused by 1 or more endemic or opportunistic fungi
 Endemic fungi  infection in healthy hosts and immunocompromised persons in defined geographic locations
o Histoplasmosis, Blastomycosis, Coccidioidomycosis
 Opportunistic  infection in patients w/ congenital or acquired defects in host defenses
o Cryptococcus, Aspergillus, Mucor, PJP, MAC
 Dimorphic fungi – blasto, histo, coccidioides
o “Yeasty beasties in body heat; bold molds in the cold”

ENDEMIC FUNGI
Histoplasmosis
 Epi: Mississippi and Ohio river valleys, Bird/bat droppings
 Micro: small, dimorphic yeast (filamentous or yeast), Intracellular – “Histo hides (within macrophages)”
 Pathophys: spores  alveoli  convert to yeast  reproduce  spread to hilar lymph nodes  rest of body  T-lymphocytes increase  granuloma 
caseation + necrosis  lesions heal w/ fibrosis
 3 types
o Acute/primary: Usually asymptomatic  complete recovery
o Chronic pulmonary (cavitary): tends to occur in abnormal lung; looks like TB on CXR  resolves slowly
o Progressive disseminated (PDH)
 T cell dysfunction  yeast continue to multiply
 Clinical: acute – fever, HSM, anemia, leukopenia, thrombocytopenia  chronic – wasting, anorexia, fever
 Most common in AIDS patients
 Dx: culture or direct visualization w/in macs, Giemsa stain, sourced from bronchoscopy/BM/peripheral smear/skin not helpful, serological studies (fungal Ag
assay, Ab)
 Tx: PDH or severe acute pulm amphotericin B + steroids x 1-2 weeks  itraconazole x 3 months – 1 year *AIDS – continue until CD4 > 350

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o Mild to moderate acute pulmonary  itraconazole x 6-12 weeks
Blastomycosis
 Epi: Soil near water in Ohio and Mississippi river valleys, DIMORPHIC
 Pathophys: initial response neutrophilic  yeast multiplies and surrounded by NTs  macs multiple  giant cell and epitheloid granulomas 
blastomycoses produce BAD-1 that downregulates Th1 responses  dissemination to organs
 Clinical: lung most common site  acute PNA(fever, chills, cough, productive sputum, crackles, consolidation)
o Chronic PNA  gradual – low-grade fever, productive cough, weight loss
o Cutaneous: Subcutaneious nodules and abscesses  papules  ulcers w/ irregular borders and crusting
 Dx: no classic CXR pattern, sputum + KOH = “Broad, big-based budding organism” 
 Tx: Itraconazole x 6 months Severe  amphotericin B + steroids  itraconazole x 1 year
Coccidioidomycosis (coccidioides immitis)
 Epi: Southwestern United States (San Joaquin Valley)
 Pathophys: arthrospores inhaled  develop into spherules  endospores released into surrounding tissues
 Types
o Primary pulmonary infection – influenza-like illness that resolves in a few weeks
o “Valley Fever” aka “desert rheumatism” – fever, arthralgia, erythema nodosum,
erythematous macular rash, night sweats, cough
o Disseminated (immunocompromised) – verrucous granuloma at nasolabial fold,
meninges, skeleton, visceral organs
 CXR: Thin-walled cavities, infiltrates, nodules, mediastinal/hilar adenopathy, pleural effusion on CXR

 Dx: ID of spherules on sputum smears (methamine silver stain)
 Tx: Uncomplicated primary infxn fluconazole or itraconaole x 3-6 months
o Disseminated to spine or not responsive to azoles  amphotericin B
o Meninges  lifelong fluconazole

OPPORTUNISTIC FUNGI
Cryptococcus (cryptococcus neoformans)
 Epi: Pigeon/bird droppings = everywhere
 Micro: thick carbohydrate capsule (dehydrates and allow it to be aerosolized)
 Pathophys: once in alveoli, yeast grows and large capsule appears (resists phagocytosis)  diminished fungicidal interferon-gamma and T- cell responses
o Antigens present to CD4 T cells  stimulate production of IL-15 + cytokines  activate CD8  granulysin cytotoxic to fungi
 RFs: T cell immune deficiency (AIDS)
 3 types
o Asymptomatic pulmonary – most common
o Primary pulmonary – fever, malaise, chest pain, cough
o Disseminated disease w/o granulomas = reactivation
 Extrapulmonary: most commonly manifests as meningitis
o Subacute illness  fever, confusion, HA (RARELY acute, nuchal rigidity, papilledema, coma)
o Dx: LP often w/ inc opening pressure *HIGH MORBIDITY!
 Dx: mucicarmine stain (specific), thick capsule appears clear on India ink stain
 Tx: Primary  fluconazole x 6 months
o Disseminated  amphotericin B + Flucytosine x 2 weeks  fluconazole x 3 weeks
o Meningitis  amphotericin B + Flucytosine x 2 weeks  lifelong fluconazole
Aspergillosis
 Micro: Septate hyphae w/ finger-like branching at acute angles 
 Allergic bronchopulmonary aspergillosis (in severe asthmatics and CF ps)
o Clinical: fleeting pulm opacities, eosinophilia and wheezing, cough up brown stuff, CXR – bronchiectasis
o Tx: steroids + itraconazole
 Aspergilloma (“fungal ball”) 
o Grow in preexisting lung cavities
o Clinical: cough, hemoptysis, dyspnea, weight loss, fatigue, fever, chest pain
o Tx: observation or surgical resection
 Invasive aspergillosis
o Halo sign on CT (lesion w/ necrotic center surrounded by ring of hemorrhage)
o Dx: histopath or galactomannan assay Tx: voriconazole
Mucormycosis (zygomycosis)
 RFs: prolonged neutropenia, severe burns/trauma, poorly controlled DM, steroids
 Rhinocerebral disease  rapidly fatal
o Ssx: HA, epistaxis, periorbital edema, vision changes, black necrotic tissue in nose/palate
 Pulmonary disease  massive hemoptysis
 Dx: Aseptate hyphae w/ wide/right-angle branching
 Tx: surgical debridement + amphotericin B
 Seen after tornados, tsunamis, blast injuries in Afghanistan
Penumoncystis jiroveci
 Most common AIDS-associated opportunistic infection in US (when CD4 count <200 cells/μL)
 Clinical: Prodrome of 1 month (fever, nonproductive cough, DOE, hypoxemia), normal lung exam (maybe insp crackles)
 CXR: Perihilar/”bat wing” opacities  reticular opacities
 Dx: CAN’T BE CULTURED, elevated 1-3-beta-d-glucan + CXR findings
 Tx: TMP-SMX x 21 days + steroids if hypoxemic
o Prophylaxis w/ TMP-SMX when CD4 <200
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Mycobacterium avium complex (MAC)
 Enter through GI tract or lung; occur in AIDS when CD4 <50 cells/μL
 Dx: blood culture
 Tx: azithromycin + ethambutol + rifampin
o Prophylaxis when CD4 <50 cells

What type of pneumonia is most common in a pt w/ HIV? Strep pneumoniae


- “This lecture has the zebras, but if you hear hoofbeats, it’s probably still horses”

Lecture 23: Restrictive Lung Disease (GEORGES)


Restrictive Diseases
 Overall decrease in lung volume and lung compliance d/t diseases of the rate controller, ventilator pump, or gas exchanger
o Intrinsic disorders: Major changes in lung parenchyma
o Extrinsic disorders: Diseases of the chest wall, pleura, or neuromuscular apparatus  Affect rate controller
Extrinsic Lung Diseases
 Extrinsic causes affect the ventilatory pump: airways, bones, muscles, peripheral nerves, and pleura involved in respiration
o Neuromuscular disease: ALS, poliomyelitis, MG, Guillian-Barre, spinal cord lesions, B/L diaphragm paralysis
o Non-NM diseases: OBESITY, chest wall trauma, kyphoscoliosis, pleural disease, pneumothorax (DECOMPRESS @ 2 ICS MID-CLAVICULAR)
 PE: Obesity, trauma, etc.; pleural disorders  tactile fremitus, percussion changes, breath sound changes
 If restrictive defect is present and patient has a normal DLCO, they have an extrinsic lung disease
Intrinsic Lung Diseases
 Intrinsic disorders affect the gas exchanger  Alveoli and their capillary network
 Cause (1) Inflammation and/or scarring of lung tissue (interstidial lung disease), or (2) Filling of air spaces with exudate & debris (pneumonitis)
 Results: Decreased compliance, hypoxemia w/ exercise or at rest, decreased DLCO (to differentiate from extrinsic)

Evaluation and Suggested Treatments


 Basics: ABCs, IV, O2, Monitor; labs, EKG, CXR, PFTs
 Extrinsic Disorders: Treatment based on the rate controller or ventilatory pump
o Critical to prevent hypoxemia and obtain airway access if needed
 Intrinsic Disorders: Treatment based on the gas exchanger
o Can be acute, subacute, or chronic
 May include: PFTs, CT/MRI of chest, bronchoscopy w/ washings, BAL, U/s or biopsy (open-lung?), VATS or exercise testing

Intrinsic Restrictive Diseases


Diffuse Interstitial Pulmonary Fibrosis
 Initial infiltration of interstitium w/ lymphocytes and plasma cells followed by
fibroblasts depositing thick collagen bundles
 Eventually destroys lung architecture  HONEYCOMB LUNG
 Clinically: mid-late-aged male smokers with dry & non-productive cough,
exertional dyspnea that progresses to SOB at rest.
 PE: Velcro Crackles on auscultation, hypoxemia, increased A-a gradient,
decreased DLCO, restrictive pattern on PFT
 Tx: corticosteroids, cytotaxan, Imuran – not sure if helpful
Pneumoconiosis
 Caused by deposition of INORGANIC matter (mineral dust) in lung macrophages and lymphatics
 Different subtypes of pneumoconiosis are caused by deposition of different types of inorganic matter
(know table)
 Eventually becomes progressive massive fibrosis, especially in the upper zones of lung
 Silicosis: crystalline-free silica
o Acute: Pulmonary alveolar proteinosis
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o Chronic: Nodular silicosis and progressive fibrosis
o CXR  EGG SHELL CALCIFICATION
o PFTs can be obstructive, restrictive, or normal
 Asbestosis: Asbestos dust in shipyards, insulators, construction workers, etc.  Lung fibrosis & pleural disease
o Pleural plaques (asbestos body) on diaphragm, parietal pleura, and interlobar fissure
o Predisposed to mesothelioma and squamous cell carcinoma of the lung
 NEW PLEURAL EFFUSION AND PLEURAL-BASED MASS (MESOTHELIOMA)
 Berylliosis: THINK AEROSPACE; Beryllium dust causing granulation formation disease that mimics sarcoidosis
 Coal worker’s: Coal dust and graphite causing chronic cough and CXR showing diffuse small rounded opacities
o Caplan Syndrome: Coal dust exposure + RA
o Multiple large cavitary nodules in the lung associated with RA
Sarcoidosis
 Systemic disease with non-caseating granulomatous tissue made up of histiocytes, giant cells, and lymphocytes
 Fibrotic changes occur in advanced disease  Respiratory failure
 Far more prevalent in AAs Tx – corticosteroids
 “A GRUELING Disease”  ACE Enzyme ^, Granuloma, RA, Uveitis, Erythema Nodosum (shin), Lymphadenopathy (B/L HILAR!), Idiopathic, Non-caseating, Vit D
increase
Hypersensitivity Pneumonitis (Extrinsic allergic alveolitis)
 Type 3 (immune complexes) or Type 4 (delayed-type) hypersensitivity reactions in response to inhaling ORGANIC dust
 Exposure  Sensitization  Acute disease (dyspnea, fever, malaise 2-4 days)  Chronic disease  Fibrosis
 THINK FARMER’S LUNG, PIGEON BREEDER’S, HOT TUB LUNG, etc.
Diffuse Alveolar Hemorrhage (DAH) and Pulmonary Vasculitis
 3 distinct patterns: Bland pulmonary hemorrhage, Diffuse alveolar damage, and Pulmonary capillaritis
 Look for high ESR, abnormal urine sediment and proteinuria, hematuria, anti-BM Abs of glomeruli (Goodpastures)
 Wegener Granulomatosis: Systemic necrotizing vasculitis of small & medium-sized vessels
o Affects upper airway, lower RT, and kidneys  Cough, chest pain, dyspnea, and hemoptysis
 Microscopic Polyangiitis: Most common cause of pulmonary renal syndrome  Rapidly progressive glomerulonephritis
 Churg-Strauss Syndrome: asthma, eosinophilia, necrotizing vasculitis  skin nodules/purpura and necrotizing granulomas
 Goodpasture Syndrome: DAH associated with anti-glomerular BM antibodies
o Dx with fluorescent anti-IgG antibodies  Attach to basement membrane
Lymphangioleiomyomatosis (LAM) (1)
 Associated with females of childbearing age or tuberous sclerosis complex
 Present with dyspnea and spontaneous pneumothorax (IN OTHERWISE HEALTHY YOUNG FEMALE)
 CXR: Mid to upper lung interstitial patterns and multiple cystic lesions
 PFTs: Obstructive and restrictive patterh
 Tx: Bronchodilators and O2. Avoid estrogen drugs
Eosinophilic Lung Diseases (2)
 Loffler syndrome: transient pulmonary infiltrates, dyspnea, dry cough – secondary to drugs or parasites
o Eosinophils are in the lung, not in the periphery (blood)
 Acute form: fever, non-productive cough, & dyspnea < 7 days with no peripheral eosinophilia
o CXR  diffuse b/l pulmonary infiltrates Lavage  Abundant eosinophils
 Chronic form: Productive cough, dyspnea, fever, night sweats, weight loss, & peripheral eosinophils
Allergic Bronchopulmonary Aspergillosis (3)
 Hypersensitivity reaction when Aspergillus colonizes aiways in patients with asthma or CF
 Fever, malaise, productive cough  Thick brown mucus plugs, possibly with hemoptysis
 Peripheral eosinophilia > 10%, with increased IgE levels, and Antibodies to aspergillus  Tx = steroids
Pulmonary Alveolar Proteinosis (4)
 Fluid build-up within the alveoli  Crazy paving: thickened intralobular and interlobular septa & foamy alveolar macs

Lecture 24: Deep Vein Thrombosis & Pulmonary Embolus (GEORGES)


Pathophysiology
 Virchow’s triad  stasis, hypercoagulability, vessel wall trauma PE arises from DVT in 85% cases
 PE usually arise from deep veins in pelvis & legs
Phlegmasia cerulean dolens – painful blue inflammation of leg
 Sx: leg intensely swollen, painful, cyanotic; may have petechiae and bullae; venous gangrene may occur
Phlegmasia alba dolens – iliofemoral thrombosis w/ intense arterial SPASM
 Leg swollen, but not tense  skin doughy and white (MILK) +/- petchiae, tends to regain pulse but then takes on appearance of ^

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*LOOK FOR CARCINOMA OF GI TRACT IF ^^ PRESENTATION*

RF: Factor V Leiden abnormality, estrogen contraceptives, malignancy, trauma,


immobility, orthopedic surgery
What to expect in Heart/Lung: V/Q mismatch, ^ alveolar dead space, release of
vasoactive substances
 RL shunt, ^ A-a gradient, lung infarct
 Saddle embolism, platelets release serotonin causing
bronchoconstriction, wheezing
Sx: Most common  new onset dyspnea at rest or exertion
 Sinus tachycardia MOST COMMON arrhythmia
 95% pt have 1 of dyspnea, tachypnea, pleura chest pain
 BRONCHOSPASM can be a presenting sx  diffuse wheezing
 Signs: cord, edema, swelling, + Homan’s sign
 Presence of hypoxemia that can’t be explained by known dz process
is PE until proven otherwise
Initial Evaluation: The Big 3 tests
 ECG: sinus tachycardia is most common arrhythmia & RBBB is most
common conduction abnormality
o S1, Q3, T3 in leads 1 & 3 = McGinn-White pattern
o V1-V4 T wave inversion & incomplete RBBB
 CXR: can be normal or abnormal
o Atelectasis, Westermark sign, Hampton’s hump (rounded
convex apex directed toward diaphragm or pleural surface
o *pts w/ dyspnea & hypoxemia w/ normal CXR should be considered for PE*

 ABG: hypoxemia, normal/low PaCO2 w/ widened A-a gradient (normal in 40% pts w/ PE)
PE Work up
 Establish Pretest probability (PTP) – based hx, PE & clinical gestalt, must assess before definitive tests
 Screening D-dimer – looks for clots, only if low/intermediate probability
 CT-A of chest/thorax or V/Q scan – NO CI in ALL TRIMESTERS OF PREGNANCY
 Duplex ultrasound of legs or cardiac TEE
Perc criteria (Pulmonary Embolism Rule-Out Criteria)
 Must meet all 8 criteria to be PERC negative Developed to combat low specific of D-dimer
 Pt >49 y/o, pulse >99 bpm, pulse ox <95%, hx of hemoptysis, pt receiving exogenous estrogen, prior dx VTE, etc – only
catches them 10%
Wells criteria will be given to us on test
 0-1 3.6% probability of PE Low risk 0-4 7.8% PE PE unlikely
 2-6 20.5% probability of PE Moderate risk >4 40.7% PE PE likely
 >6 66.7% probability of PE High risk
D-dimer = Fibrin degradation product, not specific to PE, highly sensitive quantitative or turbimetric test
 If low or intermediate pre-test probability and negative D-dimer  No PE
IF + D-dimer  CTA
 Initial diagnostic modality of choice in most facilities
 Downside: decrease sensitivity in dx sub-segmental PE, cost, & radiation exposure
Pregnant Pt
 ^ risk of VTE – most common non-traumatic cause of maternal death in developed countries
 D-dimer increases during gestational period
 Dx modality of choice = Chest-CT (safe in all trimesters)
 Tx: unfractionated or LMWH but Coumadin is contraindicated

Summary of Treatment
 Supportive care – fluid replacement for hypotension, supplemental O2, mechanical ventilation for resp fail
 Risk stratification of low (no compromise but MI injury), intermediate (stable but RV strain), high (shock)
 Standard treatment = anticoagulation followed by Vitamin K antagonists like warfarin
o HIGHLY recommended starting anticoagulation empirically w/ high risk awaiting dx imaging
o Exception: CI  use IVC filter or unstable pts who need immediate medical/surgical intervention
Tx: anticoagulation  anti-thrombins & Vit K antagonist
 Heparin & Warfarin (Vit K antagonist) except for unstable pts
o Warfarin should be continued for minimum of 5 days or until INR >/= 2.0 for at least 24-24 hours
 Thrombolytic CI: hemorrhage/ischemic stroke last 6 month, CNS damage, trauma/surgery in last 3 week, bleeds
o If thrombolytics CI: low dose TPA, catheter fragmentation, surgical embolectomy
 Who needs thrombolytics
o Massive PE (acute PE w/ hypotension (systolic BP<90))
o Sub-massive PE – stable on admission but cardiac ultrasound reveals RV dysfunction
Surgical Tx of PE
 Surgical embolectomy or thrombectomy  pts w/ PE, sustained hypotension & CI to fibrinolytic tx, catheter fragmentation
 IVC filter  pt w/ acute DVT who can’t undergo anticoagulation b/c of active bleeding or ^ bleeding risk
o i.e. Pt who has hx of DVT, been on anticoagulants  presents w/ GI bleed, hemoglobin 7, new clot  IVC filter
Pt sx w/ abnormal vitals, high pretest probability, +D-dimer, but inconclusive CTA  Lower extremity ultrasound

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If can’t get CTA b/c pt has renal fail, contrast allergy, pregnant  ventilation-perfusion lung scan
Summary
• Consider PE in any pt with unexplained dyspnea, tachypnea or chest pain.
• Work-up for suspected PE begins w/ establishment of the pretest probability.
• A negative sensitive d-dimer will exclude PE in low risk groups.
• CTA, in general, is the initial imaging study for patients with suspected PE.
• For pts with low-moderate PTP, a neg. CTA excludes the diagnosis of PE.
• V/Q scans are used when CTA unavailable or contraindicated. Indeterminate scans need to have further studies.
• High probability pts with a negative CTA need further investigation.
• Treatment of PE is with UFH or LMWH with initiation of oral warfarin.
• Fibrinolytics indicated in pts with confirmed PE & sustained hypotension

Lectures 25 & 26: Primary Lung Cancer (GOLDSCHMIDT)


Case 1: 76year old male with COPD, HTN, 60 pack year smoker. 40 lb. Weight loss in 6 months. Presents with fatigue, increasing dyspnea and right sided chest pain. He
spends ~50% of the day recumbent position. Further ROS significant for back and hip pain x 3 months. Exam is remarkable for cachexia and clubbing. Left lung sounds are
decreased at the base with dullness to percussion. Point tenderness to T3 and L2. Pain with palpation over the right greater trochanter
- Labs: CBC  Hgb 11, Plt 560, Wbc 12,000 w/ left shift Chem  Na 129, Ca 10.5, Alb 2.1, Cr 0.9, LDH 165; LFTs normal
- Pleural fluid  exudative; cytology + for squamous cell carcinoma Staging  bone scan + in spine and hip; CT – liver lesions both lobes
 Case 1
o Typically see an exudative pleural effusion (high in protein) with lung cancer masses >>>>>
o Squamous cell carcinoma used to be the most common cause of lung cancer  now adenocarcinoma (due to
unfiltered cigarettes)
o Staging = Bone scan, CT abdomen
o Tx: Lung cancer that has metastasized (All tx is PALLEATIVE  this is incurable)
 Talc pleurodesis, IV bisphosphonate (prevent further fx), rad to spine/hip (prevent fx if symptomatic)
 Do not withhold narcotics from cancer pts
 Platinum chemotherapy until progression  gives pts extra 3 or 4 months
 At progression  Afatinib  new oral tyrosine kinase inhibitor
Risk factors for lung cancer: Smoking, Environmental (2nd hand radon, pollution), Radiation exposure  RARE, asbestos/silicosis/berylliosis
Lung Cancer Screening
 Chest CT annually for 3 years in a row (reduce cancer mortality)
 Screen high risk  >55 yo, pack years >30
 Problem w/ screening is high incidence of false positives  can lead to pneumothorax if biopsy needed  problem in high risk pts
Common Symptoms
 Large airway obstruction
 Obstructive pneumonitis/atelectasis
 Dyspnea out of proportion to mass
 Pleural/pericardial effusion
 Hemoptysis
 Wt loss
 Hoarseness  recurrent laryngeal nerve
 Superior vena cava syndrome (SVC)
 Brachial plexus involvement (Superior Sulcus tumors)
o Horner’s syndrome, rib destruction, upper
extremity pain (C8, T1, T2 nerve roots)
 Hepatic metastases  wt loss + weakness
 Brain metastasis  common in small cell
o Leptomeningeal spread  pain, visual
disturbance, HA

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Common Paraneoplastic syndromes
 Hypercalcemia  PTH-RP (squamous cell carcinoma), body metastases
 Digital clubbing  humoral factors
 Hypertrophic osteoarthropathy (adenoca)
 SIADH (syndrome of inappropriate ADH)  hyponatremia
 Ectopic ACTH  Cushing’s syndrome
Histopathologies

 TNM Staging system


o T – tumor
o N – node (local, regional, distant)
o M – metastasis
o The bigger the number  the worse it is
Tx of Non-Small Cell Lung Cancer
 Stage I – IIIa  Surgery  adjuvant chemo
 Stage I –IIIa poor operative candidate (test with pulm function test)
o Radiation/chemoradiation (synergistic)
 Stage IIIb  radiation/chemoradiation
 Stage IV  Primary chemotherapy (platinum doublet vs single agent vs targeted therapy)

Case 2: 42-year-old female otherwise healthy presents with cough. She is an athlete and never smoked. Treated empirically for “bronchitis” with antibiotics and
antitussives. Chest xray after no response to Rx. Patient is felt to have worsening pneumonia. Rx new antibiotic. Chest CT ordered in the ER when she presents with
pleuritic chest pain several weeks later. Pulmonary consulted and perform bronchoscopy. BAL and transbronchial biopsy reveal atypical mucin laden cells. Presumed
diagnosis of bronchoalveolar carcinoma is made.

Inhibiting the Epidermal Growth Factor Receptor (EGFR) axis


 Problem is the firing of the tyrosine kinase inside the cell and overstimulates the cell
o Targeted by Cetuximab (acts on the extracellular side)
o Erlotinib or Getifinib on the cytosolic side
Broncheoalveolar carcinoma  subset of adenocarcinoma
 Many have an EGFR mutation (common 2ndry mutation = t790m)
 Mimics pneumonia, goes to weeks-months undiagnosed (nonsmokers)
 Often seen in ASIANS

Case 3: 64 yo male admitted for ches pain and a-fib. 100 pack year smoker. Dx w/ MI in the ER. Screening CXR shows RUL mass. CT chest and upper abd shows 3 cm
mass and mediastinal invasion. PET  inc uptake in mass and ipsilateral hilum, but no other locations. Pulm performs bronchoscopic biopsy  neuroendocrine
carcinoma favoring small cell carcinoma.
Small Cell Carcinoma – central mass in smokers
 Tx: Very sensitive to chemotherapy (platinum based drug i.e. cisplatin or carboplatin + topoisomerase inhibitor i.e. etoposide) combined w/ radiation
o NO SURGERY
 Metastasis  Neuroendocrine tumor
o Likes to metastasize to the brain (sanctuary site)
 Risk factors: Smoking
 Staging: “Limited” (confined primarily to thoracic cavity) or “extensive” (distant sites)
 Paraneoplastic Syndromes
o Ectopic ACTH, SIADH (HYPONATREMIA), Inflammatory polyneuropathy (ab against myelin), Cerebellar degeneration (anti-Hu)
o Eaton-Lambert Myasthenia Gravis  proximal muscle weakness

Case 4: WALTER WHITE. Biopsy is performed  mod-differentiated adenocarcinoma. PET scan  no sites outside ipsilateral mediastinum. Good lung function. Course
of chemo-radiation prescribed to shrink tumor and aid in surgical resection. Subsequent restating  biopsy of the lung reveals lung adenocarcinoma w/ novel fusion
gene ALK-EML4. Begins Crizotinib w/ very little side effects and improvement in scans.
Lung Surgery – lobectomy, pneumonectomy, sleeve resection, wedge resection, VATS
 Lobectomy is the most common
 Can live with only 1 lung
Anaplastic Lymphoma Kinase - EML4 (ALK-EML4)
 Can affect younger pts w/o smoking hx
 Novel fusion gene seen in non-small-cell lung cancer
 Crizotinib will act on this gene

Case 5: 78 yo power company worker develops SOB. PMH significant for COPD, CAD. Asbestos exposure on the job. Right lung breath sounds
diminished and dull to percussion. CXR and CT ordered  pleural plaques
Mesothelioma
 Spindle cell neoplasm, positive for claretinin
 Associated with asbestos
 Tumor of the pleural and peritoneal lining
 Sx: insidious dyspnea (on background of lung scarring), pleural effusion, rind forms  restricted lung fxn)
o POOR response to chemo or radiation
o Spread: SVC syndrome, pericardial tamponade, cord compression
 Better prognosis: <65, epithelial histology, early stage disease, good performance status, incidentally found
Conclusions
 Lung cancer heterogeneous group of histologic types & molecular subtypes
 High suspicion for cancer in smokers (esp those that did not quit before 40 yo)
 Screening now through SPIRAL CT
 Lung cancer diagnosis + tx = team effort
 Prognosis poor with some exceptions
o Immunotherapy starting to change this
o Immunotherapy affects CYTOTOXIC T-CELLS

Lecture 27: Pulmonary Vascular Disease (BOLIN)


*SAYS HE WILL ASK ABOUT 3 Q’S ON PULM HTN AND 2 ON PULM RENAL SYNDROME*
Normal Pulm Hemodynamics
 Low pressure – 6-8 mm Hg large ^ BF w/ exercise DOESN’T ^ resistance across pulm vascular bed
Pulm HTN
 Decrease flow resulting from ^ vascular resistance leading to R heart failure
 Def: mean pulm artery pressure (mPAP) > 25 mm HG at rest  determined by R heart catheterization
 Cause: ^ pulm venous pressure (CHF), ^ pulm blood flow (prego), ^ pulm vascular resistance (hypoxia, smoke)
o LR shunt w/ chronically ^ flow there is remodeling of arteriolar wall
o Vasoconstriction from chronic hypoxemia via high altitude, COPD, pulm fibrosis, sleep apnea
 **O2 no longer able to get in blood and you feel fatigued (can get plexiform lesions)
o Vascular obstruction: recurrent pulm emboli or schistosomiasis
 Types: idiopathic (women), Familial (AD, BMNPR-2 gene), 2nd to disease status (CHD, cocaine, HIV, portal HTN)
 Sx: inability to ^ CO during exercise, DYSPNEA ON EXERTION, syncope, chest pain, lethargy, FATIGUE (WORST SX), edema
o *most people will have been treated for something else (hypothyroid, depression, etc.)  take unnecessary meds away
o R upper quadrant pain (can’t get blood out of portal veins - Liver)
o Progressively less mobile (less and less CO until you have sx at rest)  until die in bed
 PE: ^ 2nd heart sound, RV lift/heave, ^ jugular venous press, distended liver, peripheral edema, RV S3 gallop
o JVD determined by having pt body elevated not just lifting the neck
Pulm HTN Dx evaluation  confirm that PH exists, determine severity, determine cause, WHO
Class
 CXR – central vessels enlargement or R heart enlargement
 EKG – RBBB or R axis deviation
 ECG – utilizes Doppler signal to estimate R atrial systolic pressure (*look for jet
lesions)
 Determine if RV enlarge or paradoxical septal bulge, determine if LVSD is present
 R heart catheterization – GOLD STANDARD w/ mPAP >25 mm Hg & 30 mm Hg w/
exercise (6-8 is normal)
 Rules out L heart disease & L>R atrial shunt, gives baseline to determine response to tx
Additional Testing
 Pulm Fxn testing – ID underlying obstructive/restrictive lung dz (lung volume <50%)
o *thoracic/rib dysfunctions have shown restrictive patterns
 Diffusion capacity of Lung for Carbon Monoxide (DLCO) – usually LOW w/ restricted pattern of PFTs in PH = DIAGNOSTIC FOR PH
 Overnight oximetry – hypoxemia is potent constrictor of pulm vascular bed (60-70% over 2-3 hrs in the night  if uncorrected would get dementia)
 Polysomnography – asked about obstructive sleep apnea
 V/Q scan – suspected pts evaluated for chronic venous thromboembolic dz (“gunshot pattern”)
 6 minute walk test (6MWT) – healthy men walk 580m & women walk 500m (sensitive test but not specific)
 HIV, LFTs – portopulmonary HTN, ANA, Ant-DNA, SCL-70, anti centromere
WHO classification
 Group 1 – PAH  mPAP of 25 & PCWP <15, idiopathic or familial PAH, associated w/ anorexia, scleroderma/SLE/RA, HIV, rec drugs, portal HTN
o Prognosis: once sx, median survival is only 3 years, die w/in 1 year w/out tx
 Group 2 – 2nd to LHD, mPAP > 25 & PAWP > 15 w/ normal/reduced CO
 Group 3 – 2nd to chronic lung dz
 Group 4 – chronic thromboembolic dz, hx of DVT & PE
 Group 5 – unclear/multifactorial, Tx: advanced therapy
**Worse Prognosis  WHO group 1, male >45 y/o, WHO functional class 3 or 4, failure to
move to lower fx class w/ tx
Tx
 Advance therapy, supplement O2, CPAP, pulm rehab, anticoagulation, Ca blocker
(AVOID verapamil)  only small % of pts respond to them!
 Soluble guanylate cyclase (Adempas) – interact w/ NO to relax pulm arteries and CI in
pregnancy
 Prostanoids (potent vasodilator), Endothelin Rec Antagonist (endothelin –
vasoconstrictor)
 Phosphodiesterase 5 inhibitor (Viagra) – prolong vasodilatory effects of NO
 Group 2-4  2 = Bosentan/Sildenafil 3 = Bosentan &/or Sildenafil +/- Flolan 4 = Flolan
 In end stage PAH  heart & lung transplant
Pulmonary Renal Syndromes- Goodpastures, Wegener, SLE
 Sx: rapidly progressive onset of cough, dyspnea, fever & hemoptysis  present like pt w/ pneumonia in ARDS (only hint is that they have CT
disorder)
 Labs: CXR w/ diffuse patchy alveolar infiltrates, leukocytosis, falling Hb, elevated creatinine, + ANCA, cANCA, Anti GBM Ab, anti-DNA, drug screen
Goodpastures
 Rapidly progressive glomerulonephritis 2nd to circulating Ab against basement membrane (type 4 collagen)
 Younger adults <30 present w/ full constellation of sx whereas older adults > 50 have primarily glomerular dz
o Crescent formation: linear IgG immune-fluorescence of glomeruli
 Present: resp failure & resemble pneumonia w/ ARDS, frothy sputum (absence purulent sputum)
 Clues: elevation of serum creatinine (kidney), mild anemic, bronchoalveolar lavage
 Labs: anti GMB antibody, kidney biopsy, immunofluorescence will reveal linear deposition of IgG
 Tx: Plasmapheresis to remove offending antibodies, prednisone & cyclophosphamide decrease Ab production
o HAVE TO DISTINGUISH FROM PNEUMONIA BC W/O TX UNDERLYING ISSUE, WILL
DETERORIATE AND DIE

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