Exam 2 Study Guide 2018
Exam 2 Study Guide 2018
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.)
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
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
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
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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)
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
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*LOOK FOR CARCINOMA OF GI TRACT IF ^^ PRESENTATION*
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
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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
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.
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