The document discusses a clinical case of a 41-year-old man presenting with fever, diarrhea, and respiratory symptoms, ultimately diagnosed with acute respiratory failure due to influenza A infection and sepsis. The management included hydration, antibiotics, and ventilatory support, highlighting the complexities of acute respiratory distress syndrome (ARDS) management. It also outlines the definition, pathogenesis, diagnosis, and treatment approaches for ARDS, emphasizing supportive therapies and lung-protective ventilation strategies.

1. Clinico-Pathologic
Conference
Khushboo Gandhi, MD
St. Luke’s Hospital Internal Medicine Residency
September 28, 2017

2. History of Present Illness
• A 41 year old man complained of fever,
diarrhea, and generalized myalgia.
• He had been doing well until 3 days ago when
he started to have fever going to 103.
• His wife stated that she had given him Tylenol
for his symptoms but he began to have
diarrhea.
• He noted cough occasionally productive of
greenish phlegm and some pleuritic pain with
deep breath.
• There was no abdominal pain or nausea. He felt
weak and exhausted and came to the ER.
• As an oral surgeon there had been no recent
changes in his practice. No recent travel,
immobilization, or tick exposure.
• Denies unusual or unpasteurized foods. Drinks
well water which has been filtered.
• High grade fever with greenish productive
cough associated with pleuritic chest pain,
weakness and exhaustion x 3 days
• Diarrhea - one time episode??
• No abdominal pain or nausea/vomiting
• No travel, immobilization – at low risk for DVT
and PE
• No tick exposure; Pets?
• Oral surgeon - sick contacts??
• No recent change in his practice - assume no
change in instruments or unusual exposure to
toxic inhalants.
• Sore throat??
• Hemoptysis??
• Year and month of presentation – 2009??

3. Other Histories
• PMH: Morbid obesity, Hypertension, Fibula Fx
with internal fixation 5 years ago
• MEDICATIONS: Zoloft, lisinopril, atenolol, aspirin,
and amlodipine.
• ALLERGIES: None known
• SH/FH: Does not smoke. Rarely drinks any
alcohol. He is a dentist married with 2 children.
No FH of blood clots.
• REVIEW OF SYSTEMS: Review of systems in the
last 6 months was unremarkable. Obese with
stable weight. Hx daytime sleepiness and dozing.
• FAMILY HISTORY: Noncontributory.
• Obese, daytime sleepiness and dozing –
Obstructive Sleep Apnea/CPAP??
• Medications: How long has he been taking
those medications? Any new medication
recently started?
• No weight loss
• Allergies??
• Anyone in family or at work sick?
• Vaccination??

4. Physical Examination
• BP 89/55, P 90, R 18, T 39.5, BMI 42, O2 sat 95%
on RA.
• The patient is lying in bed somnolent at times but
arousable. No icterus.
• PERL, SKIN - No rash.
• Mouth/Thr - Clear with good dentition. Congested
throat. Neck: No cervical or supraclavicular
lymphadenopathy.
• Lungs: Distant BS but crackles at bases L>R, no
wheezing.
• Cardiovascular: No JVD noted. RRR and no murmur
or gallop.
• Abdomen: Soft, obese. not tender, NBS, no
organomegaly. Genital: Normal
• Ext: No edema, cyanosis or clubbing
• Neuro: No focal deficits noted, sleepy but oriented,
coherent
• Febrile
• MAP – 66 mm hg - Borderline
hypotension
• Encephalopathic?
• Congested throat – Pharyngitis?
Tonsillitis? Exudates?
• Neck stiffness?

5. Labs & Imaging
CMP
Sodium 133
Potassium 3.8
Chloride 92
CO2 30
BUN 39
Cr 2.0 Baseline?
Glucose 153
Calcium 8.3
Total Protein 6.3
Albumin 3.1
Alkaline
Phosphatase
59
AST 88
ALT 34
TBili 0.1
Lactic Acid 1.2
ESR 44
CRP 28
CBC
WBC 7.7
Hb 14.7
Hct 41
Platelets 140
PMN 84% Left shift
L 12%
M 4%
Other tests
Legionella urinary Ag
Negative
Monospot
Gr A Strep screen
Influenza rapid screen
Blood cultures
Chest X ray – Bilateral infiltrates
primary bases, no effusion
Left shift WBC, Elevated ESR and
CRP - Systemic inflammatory response
Mild Hyponatremia
Acute renal failure
Borderline thrombocytopenia – likely a
response to sepsis
Hyperglycemia

6. Hospital Course
• Initially admitted to general medicine floor,
hydrated and given Levaquin and Flagyl.
• Amount of fluids??
• When seen the morning after admission he was
febrile and hypotensive with BP 70-80.
Examination was otherwise unchanged.
• There had been no further diarrhea.
• He was transferred to the ICU where hypoxia
was documented.
• On nasal CPAP his ABG showed pH 7.35, pO2
47, pCO2 55 on 15 liters - Assume FiO2 100%
• Repeat CXR showed somewhat denser bilateral
infiltrates.
• Cr 1.5. He was intubated and placed on
ventilator.
• Antibiotics were changed to Levaquin, Cefepime
and vancomycin.
Repeat Legionella Negative
MRSA nasal screen Negative
Resp culture Few wbcs and rare growth of
yeast
Respiratory virus culture Positive for influenza A, CMV
negative
Pneumocystis DFA Negative

7. Chest X Ray
No Kerley B Lines
Diffuse bilateral alveolar
infiltrates in the middle and
lower lung zones
No Cardiomegaly
Clear Costophrenic Angle
No evidence of pleural
effusion
Trachea in midline
ET tube in appropriate
position
No evidence of
pneumothorax

8. Problem List
• Acute Hypoxemic and Hypercapnic Respiratory Failure
• False negative rapid influenza screen and positive influenza A viral culture -
Influenza A infection (seasonal or 2009 pandemic H1N1?)
• Sepsis with septic shock? - SOFA Score 8
• Hypotension despite hydration?, vasopressors required?
• Acute renal failure (No history of previous renal disease)

9. What do you think is the likely cause of his
respiratory failure and how would you
manage the patient?

10. Acute Respiratory Failure

11. Types of Respiratory failure
Type II
Type I
Type IV
Type III
Acute Hypoxemic
Respiratory Failure
Acute Hypercapnic
Respiratory failure
RF due to Shock
Hypo perfusion of
Respiratory muscle
Alveolar flooding and
intrapulmonary shunt physiology
Alveolar hypoventilation and
inability to eliminate CO2 effectively
Lung atelectasis
Post Operative RF

12. Type I Acute Hypoxemic Respiratory Failure
No h/o HF but possible,
amount of IV fluids?
Type I Acute Hypoxemic
Respiratory Failure
Pulmonary edema
Elevated pulmonary microvascular
pressures:
HF and Intravascular volume overload
ARDS
low-pressure
pulmonary edema
Pneumonia
Alveolar
hemorrhage

13. Type II Acute Hypercapnic Respiratory Failure
Normal RR
OSA?
?OSA
Fatigue
Alveolar edema
Atelectasis
Sepsis
No COPD,
Asthma,
wheezing
Alveolar hypoventilation &
inability to eliminate carbon
dioxide effectively
Type II Respiratory Failure
impaired central
nervous system (CNS)
drive to breathe
Drug overdose, brainstem injury,
sleep-disordered breathing, and
severe hypothyroidism
Respiratory
muscle
weakness
Impaired
neuromuscular
transmission
(e.g., myasthenia
gravis, Guillain-
Barré syndrome,
amyotrophic
lateral sclerosis)
Respiratory
muscle
weakness (e.g.,
myopathy,
electrolyte
derangements,
fatigue)
Increased load on
the respiratory
system
Resistive loads
(e.g.,
bronchospasm)
Reduced lung
compliance (e.g.,
alveolar edema,
atelectasis, auto-
PEEP)
Reduced chest
wall compliance
(e.g.,
pneumothorax,
pleural effusion,
abdominal
distention)
Increased minute
ventilation
requirements
(e.g., pulmonary
embolus with
increased dead-
space fraction,
sepsis).

14. A physiology-based algorithm for acute
hypoxemic respiratory failure.
Principles and Practice of Hospital Medicine, 2e
A-a O2 Gradient = [ (FiO2) × (Atmospheric
Pressure - H2O Pressure) - (PaCO2/0.8) ] – PaO2
Expected A-a Gradient for his age - 14.3 mm Hg
His A-a Gradient - 597.3 mm Hg

15. Differential Diagnosis
Acute Respiratory Distress
Syndrome (ARDS)
Viral, atypical, opportunistic
and fungal
Diffuse Infection
Acute LHF and Acute on
Chronic CHF
Cardiogenic
Pulmonary Edema
Inflammation
DAH, Hypersensitivity
pneumonitis, Acute
eosinophilic pneumonia,
Cryptogenic pneumonia

16. Acute Respiratory Distress Syndrome (ARDS)
History
• Fifty years ago, Ashbaugh and colleagues described 12 patients with tachypnea, refractory
hypoxemia, and diffuse opacities on chest radiographs after infection or trauma.
• In 6 of the 7 patients who died, autopsy findings showed prominent hyaline membranes lining the
alveolar spaces of the lungs which was previously thought to be specific for the respiratory distress
syndrome of the newborn. Thus, the term adult (or acute) respiratory distress syndrome (ARDS) was
proposed.
• Four major definitions of ARDS have evolved over the years
• The Berlin definition, proposed in 2012

17. Berlin Definition of the ARDS
N Engl J Med 2017;377:562-72.

18. Severe Hypoxemia resistant to
oxygen therapy (CPAP)
Exam: no signs of HF (JVD, Peripheral
edema, S3 gallop)
CXR findings – BL alveolar infiltrates,
normal heart size, no pleural effusions
Onset within 7 days of clinical insult
PaO2/FiO2: 47 mmHg à Severe ARDS
ARDS
??
Favors
Against

19. EPIDEMIOLOGIC FEATURES
• ARDS range from 10 to 86 cases per 100,000, highest rates reported in Australia and the United
States.
• ARDS is likely to be underreported in low-income countries because of limited resources to diagnose
• High-income countries, ARDS remains under recognized.
• One explanation - may be disagreement about the nature of the radiographic opacities that support
the diagnosis.
• Increased risk of ARDS:
• Chronic alcohol abuse, hypoproteinemia, advanced age, increased severity, and extent of injury or
illness as measured by injury severity score (ISS) or APACHE score, hypertransfusion of blood
products, and cigarette smoking.

20. PATHOGENESIS
The Healthy Lung and the Exudative
Phase of ARDS.
Accumulation of
neutrophils & monocytes
Release toxic
mediators
Loss of barrier
function, interstitial and
intraalveolar flooding
Activation of alveolar
macrophages
Release of potent pro
inflammatory mediators
and chemokines
Injury to alveoli and
microvasculature
Tumor necrosis factor
mediated expression of
tissue factor
Platelet aggregation
microthrombus
formation, intraalveolar
coagulation
Hyaline-membrane
formation

21. Proliferative & Fibrotic Phase
Proliferative: Aims to restore tissue homeostasis
Prolonged prolifera.on of
fibroblast
Extensive basement membrane damage
and inadequate reepithelializa.on
Transient expansion of resident
fibroblasts and the forma.on of a
provisional matrix
Reestablishes epithelial integrity
Reabsorp.on of alveolar edema
Proliferative Phase
Fibrotic Phase
Does not occur
in all patients
Linked to prolonged
mechanical ventilation &
increased mortality
In some patients

22. Time course of ARDS
Fishman's Pulmonary Diseases and Disorders, 5eSchematic representation showing time course of evolution of the acute respiratory distress syndrome (ARDS).
Interstitial and alveolar edema
hemorrhage
Hyaline Membrane Interstitial and alveolar inflammation
fibrosis

23. Failure of oxygenation in ARDS
Shunt Physiology in ARDS
Fishman's Pulmonary Diseases and Disorders, 5e

24. Clinical Presentation
• The development of ARDS - within 12 to 72 hours of the predisposing event
• Inflammatory changes in the lung decrease lung compliance, increases work of breathing, and patients often
become anxious, agitated, and tachypnic.
• If breathing ambient air or low-flow supplementary oxygen, ABG - PaO2 less than 50 to 55 mm Hg and SpO2
of less than 85%.
• The hallmark of ARDS is hypoxemia that is resistant to oxygen therapy because of the large right-to-left shunt
Fishman's Pulmonary Diseases and Disorders, 5e

25. Approach to Clinical Diagnosis
CHEST RADIOGRAPH
• Diffuse, bilateral alveolar infiltrates consistent with pulmonary edema
• Early in the course of the disorder, the infiltrates associated with ARDS may be variable
o Mild or dense, interstitial or alveolar, patchy or confluent
o Radiographic infiltrates may not correlate well with the degree of hypoxemia, may be interpreted as
pneumonia or segmental atelectasis
Fishman's Pulmonary Diseases and Disorders, 5e

26. Chest CT and plain radiograph in ARDS.
A Chest CT scan - asymmetric lung
injury, with dense consolidation at
the right base, patchy alveolar
infiltrates in the right anterior lung
field, and patchy ground-glass
infiltrates throughout the right lung.
B Chest radiograph obtained
concurrently - dense infiltrates at
right base, patchy infiltrates in the
right upper lung zone, and more
subtle infiltrates in the left lung are
demonstrated.
Cardiogenic edema: increased heart size, increased width of the vascular pedicle,
vascular redistribution toward upper lobes, the presence of septal lines (Kerley
lines), or a perihilar (bat's wing) distribution of the edema.
Lack of these findings, in conjunction with patchy peripheral infiltrates that extend
to the lateral lung margins, suggests ARDS.
Fishman's Pulmonary Diseases and Disorders, 5e

27. LABORATORY STUDIES
• No laboratory test is specific for the diagnosis of ARDS
• ABG: PaO2/FiO2 is markedly abnormal in patients with ARDS
• Cardiac enzymes - results should be interpreted in conjunction with electrocardiographic findings
• BNP – ED
• > 500 pg/mL indicates that CHF is likely with a PPV greater than 90%.
• < 100 pg/mL suggests that congestive heart is unlikely with a NPV greater than 90%
• Interpretation of an elevated BNP in critically ill patients is problematic - renal failure, sepsis
• Echocardiogram - to r/o cardiogenic pulmonary edema
• BRONCHOALVEOLAR LAVAGE - to rule in or rule out acute processes that may have specific therapies.
• Acute eosinophilic pneumonia, Diffuse alveolar hemorrhage
• LUNG BIOPSY - Routine lung biopsy is not recommended in ARDS
• Should be considered if alternative etiologies of respiratory failure cannot be adequately excluded
Fishman's Pulmonary Diseases and Disorders, 5e

28. TREATMENT AND PREVENTION
Supportive Therapy
• Identification and treatment of the underlying cause
• Sepsis-associated ARDS - early resuscitation, appropriate antibiotic agents, and source control
• Limiting further lung injury through
1. Lung-protective ventilation
2. Conservative fluid therapy
Fishman's Pulmonary Diseases and Disorders, 5e

29. Lung Protective Ventilation Strategies
Protective ventilation approach is safe and offers the
best chance of a good outcome
1.Set a target tidal volume close to 6 mL/kg of ideal
body weight.
2.Prevent plateau pressure (static pressure in the
airway at the end of inspiration) exceeding 30 cm
H2O.
3.Use the lowest possible fraction of inspired oxygen
(Fio2) to keep the Sao2 at ≥90%.
4.Adjust the PEEP (at least 5 cmH2O) to maintain
alveolar patency while preventing over distention
(Volutrauma) and closure/reopening (atelectrauma).
With the application of these techniques, the mortality
rate among patients with acute hypoxemic respiratory
failure has decreased to ~30% from close to 50% a
decade ago.

30. Prone Positioning ??
Early trials demonstrated prone positioning increased oxygenation, but this did not translate into
reduced mortality.

31. • Post hoc analyses of subgroups with more severe lung injury suggested benefit to prone positioning.
• Recommendation: Prone positioning for more than 12 h/d in severe ARDS.
• Improving ventilation–perfusion matching, increasing end-expiratory lung volume, and decreasing VILI by more uniform
distribution of tidal volume through lung recruitment and alterations in chest wall mechanics.

32. Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) ??
Initial results were disappointing – after more encouraging reports from 2009 H1N1 Pandemic its use is growing.
Further research is needed to clarify the potential efficacy of ECMO for patients with severe ARDS as well as with mild to
moderate ARDS

33. Should Patients with ARDS Receive Higher, as Compared with
Lower, PEEP?
• Higher PEEP - improve alveolar recruitment, reduce lung stress and strain, and prevent atelectrauma in some
patients with ARDS,
• Risks - injury from end-inspiratory alveolar over distention, increased intrapulmonary shunt, increased dead
space, and higher pulmonary vascular resistance leading to cor-pulmonale.
• Higher versus lower PEEP strategies were evaluated in eight RCTs

34. Recommendation: Adult patients with moderate or severe ARDS receive higher rather than
lower levels of PEEP

35. Should Patients with ARDS Receive Recruitment Maneuvers?
• Increased lung weight from interstitial and alveolar edema - Dependent
atelectasis
• Increased lung injury during mechanical ventilation.
• RMs - transient elevations in applied airway pressures - open (“recruit”)
collapsed lung and increase the number of alveolar units participating in
tidal ventilation
1. Prolonged high continuous positive airway pressure (30–40 cm H 2 O)
2. Progressive incremental increases in PEEP at constant driving pressure
3. High driving pressures
• Benefits: reduces intrapulmonary shunt and increases pulmonary
compliance
• Complications - hemodynamic compromise and barotrauma.
• Evaluated in six RCTs
• Associated with lower mortality, higher oxygenation (PaO2/FiO2 ratio) at
24 hours, and reduced the need for rescue therapy.
• Not significantly associated with barotrauma and rates of
hemodynamic compromise.
• Recommendation - Adult patients with ARDS receive RMs
Am J Respir Crit Care Med. 2017 May 1;195(9):1253-1263.
CT scan of a characteristic patient. (A) In ZEEP shows an important loss of
aeration in the left lung and slight diffuse loss of aeration in the right lung.
PaO2/FiO2 =171 mmHg; (B) acquired with a positive end expiratory pressure of 11
cmH2O showing no change in left lung and an increase in lung aeration of the right
lung. PaO2/FiO2 =171 mmHg; (C) acquired at the end of recruitment maneuver
(RM) between 35 and 40s. All the lungs were reopened. PaO2/FiO2 =342 mmHg;
(D) 10 minutes after RM with the same PEEP of 11 cmH2O. The effect of RM was
maintained. PaO2/FiO2 =335 mmHg. The level of PEEP used was unable to open
the lung but enough to keep the lung open. ZEEP, zero end expiratory pressure;
PEEP, positive end-expiratory pressure.
R
R
R
R

36. Should Patients with ARDS Receive High-Frequency Oscillatory
Ventilation (HFOV) ?
• Novel mechanisms of alveolar ventilation, permitting the delivery of very small
tidal volumes at higher mean airway pressures.
• HFOV is essentially a vibrating CPAP machine
• Small tidal volumes (1-4mL/kg)
• Delivered at high frequencies (3-15 Hz) with an oscillatory pump
• Maintains constant lung recruitment
• Aims to prevent lung injury from over distension and loss of recruitment
(atelectrauma)
• Indications
• Oxygenation failure: requiring an FiO2 > 0.7 and PEEP >14 cmH20
• Ventilation failure: pH < 7.25 with VT 6mL/kg and plateau pressure > 30cmH20
• Part of trial
• Evaluated in six RCTs - no significant difference in mortality for patients in the
HFOV versus control group
• HFOV not be used routinely in patients with moderate or severe ARDS
Am J Respir Crit Care Med. 2017 May 1;195(9):1253-1263.

37. FLUID MANAGEMENT
•Maintaining a low left atrial filling pressure minimizes pulmonary edema
•Shortens ICU stay and the duration of mechanical ventilation
•Associated with a lower mortality rate
•Aggressive attempts - to reduce left atrial filling pressures with fluid restriction and diuretics.
NEUROMUSCULAR BLOCKADE
•Sedation alone can be inadequate for the patient-ventilator synchrony required for lung-protective ventilation
•Early neuromuscular blockade (with cisatracurium besylate) for 48 h increased the rate of survival and ventilator-
free days without increasing ICU-acquired paresis.
Fishman's Pulmonary Diseases and Disorders, 5e

38. Common Direct and Indirect Precipitating Causes of ARDS
Direct Precipitating Causes Indirect (Systemic) Precipitating Causes
Aspiration of gastric fluids Acute pancreatitis
Bacterial pneumonia (diffuse), e.g.,
Legionnaires’ disease
Blood transfusions with transfusion-related
acute lung injury (TRALI)
Chest trauma with lung contusion Post-cardiopulmonary bypass
Near drowning Primary graft failure of lung transplantation
Pneumonia due to Pneumocystis jirovecii Severe sepsis and septic shock
Toxic inhalations, e.g., smoke inhalation,
inhaled crack cocaine
Toxic ingestions, e.g., aspirin, tricyclic
antidepressants
Viral pneumonia, e.g., influenza, severe acute
respiratory syndrome (SARS)
Trauma with multiple fractures and the fat-
emboli syndrome
Fishman's Pulmonary Diseases and Disorders, 5e
Pneumonia, aspiration of gastric contents, and sepsis together account for more than 85% of cases of ARDS in recent clinical trials.

39. 01
02
03
04
05
Influenza A Infection, H1N1?
Severe sepsis & septic shock
Legionnaires’ Pneumonia
Pneumocystis jirovecii
Severe Acute Respiratory Syndrome
(SARS)
Potential causes of ARDS in this patient

40. Influenza A infection
Seasonal or Pandemic H1N1?

41. Pandemic H1N1 influenza ('swine influenza')
• Clinical symptoms
• Fever, headache, cough, sore throat, myalgia, chills, and fatigue;
• Vomiting and diarrhea were also common, both of which are unusual features of seasonal influenza.
• Disease severity ranged from mild influenza-like illness to multi organ failure with severe hypoxemia
• Many hospitalized patients had infiltrates suggestive of pneumonia or acute respiratory distress syndrome
(ARDS).
• Common findings on chest radiography - patchy consolidation or ground glass opacities, with or without
consolidation; lower lung zone predominance, peripheral and central perihilar areas
• Autopsy findings of patients who died from pandemic H1N1 influenza A infection - Diffuse alveolar damage
and viral infection of alveolar lining cells. Bacterial coinfection was detected in a proportion of cases.
• Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) was the most sensitive and specific test
for the diagnosis of pandemic H1N1 influenza A virus infection.
• Rapid antigen and immunofluorescent antibody tests – varied sensitivity, and do not distinguish between
pandemic and seasonal strains of H1N1 influenza A.
• Confirmation of pandemic H1N1 influenza A infection could only be made by rRT-PCR or culture.

43. Clinical presentation
Respiratory culture positive -
Influenza A (H1N1?)
Many reports of H1N1 causing ARDS
Oral surgeon - At high risk for
exposure to sick contacts
False negative rapid screen
Rapid screen was sensitive in only
39% cases of H1N1 influenza (2009)
rRT-PCR?
ARDS due to H1N1 Influenza (‘swine influenza’)
Identification on viral
culture ??
Favors
Against

44. Legionnaire’s Disease (Pneumonia)
• First recognized in 1976 during an outbreak at an American Legion Convention in
Philadelphia
• Common cause of both community-acquired and hospital-acquired pneumonia
• Transmission: Inhalation of aerosols, aspiration of water contaminated with the organism.
• Clinical presentation:
• Fever > 104ºF
• Mild slightly productive cough, hemoptysis (sometimes), chest pain.
• GI symptoms - prominent with diarrhea, nausea, vomiting, and abdominal pain.
• Lethargy with headache and occasionally stupor.
• Physical examination - rales with subsequent signs of consolidation.
• Other findings - DIC, glomerulitis, rhabdomyolysis, various rashes, and neuropathies
• Labs: Renal and hepatic dysfunction, thrombocytopenia, leukocytosis,
hypophosphatemia, hyponatremia (serum sodium <130 mEq/L), hematuria, proteinuria.
• CXR: Common pattern patchy unilobar infiltrate that progresses to consolidation, pleural
effusions common. Can present with diffuse BL alveolar infiltration.
• Culturing for Legionella spp is the single most important laboratory test.
• Urinary antigen testing is rapid, sensitive, specific, and inexpensive, but is only useful for
the diagnosis of L. pneumophila type 1 infection (which accounts for 90 percent of
community-acquired Legionella infections in the United States).
• Rx: Azithromycin or a fluoroquinolone is the treatment of choice; Addition of rifampin may
be required
The chest radiograph shows multiple bilateral
airspace opacities. There is also a basal right
pleural effusion. Normal cardiac profile.
Case courtesy of Dr Sigmund Stuppner,
Radiopaedia.org, rID: 46812

45. Fever
Diarrhea (Single Episode?)
Neurologic findings, especially
confusion
Hyponatremia but not <130
Thrombocytopenia
Renal dysfunction - ?could be
multifactorial
Failure to respond to β-lactam drugs
(penicillins or cephalosporins) and
aminoglycoside antibiotics – pt did
not receive initially
ARDS due to Legionnaire’s Disease (Pneumonia)
Not very high fever (>104F)
No abdominal pain, nausea or
vomiting
Drinks filtered well water – but not at
risk of aspiration?, anyone in family
or at work also sick?
CXR: most common pattern is a
patchy unilobar infiltrate that
progresses to consolidation
Pleural effusions common
Negative urine antigen test x 2 (Sen
70%)
Culture with special media - buffered
charcoal yeast extract (BCYE)??
Favors
Against

46. Pneumocystis jirovecii Pneumonia
• Immunocompromised individuals (HIV, hematopoietic cell and solid organ
transplant recipients; those with cancer; and those receiving glucocorticoids,
chemotherapeutic agents, and other immunosuppressive medications)
• Patients without HIV infection - glucocorticoids combined with other
immunosuppressive therapies (eg, cyclophosphamide) and other defects in
cell-mediated immunity.
• Presents as fulminant respiratory failure associated with fever and dry cough.
• CXR: diffuse, bilateral, interstitial infiltrates, but other patterns may be seen.
• Diagnosis:
• Microbiologic identification - induced sputum or bronchoalveolar lavage
(BAL) fluid
• Identification of the organism by tinctorial (dye-based) staining, fluorescent
antibody staining, or polymerase chain reaction (PCR)-based assays
• Negative Pneumocystis DFA (false negative if organism load is low??)
• HIV??
• Bronchoscopy and BAL??
Posteroanterior chest x-ray of PJP
demonstrating extensive bilateral
basilar lung involvement.

47. Severe acute respiratory syndrome (SARS)
• Serious, life-threatening viral infection caused by a previously unrecognized virus from the Coronaviridae
family, the SARS-associated coronavirus (SARS-CoV).
The clinical case definition used by the WHO includes:
1.A history of fever or documented fever
2.One or more symptoms of lower respiratory tract illness (cough, difficulty breathing, shortness of breath)
3.Radiographic evidence of lung infiltrates consistent with pneumonia or acute respiratory distress syndrome
(ARDS) or autopsy findings consistent with the pathology of pneumonia or ARDS without an identifiable cause
4.No alternative diagnosis fully explaining the illness
Laboratory diagnostic tests that are required include one or both of the following:
1.Detection of virus by an assay for viral RNA (rRT-PCR) present in two separate samples or by virus culture from
any clinical specimen.
2.Detection of antibody by enzyme-linked immunosorbent assay and/or immunofluorescent assay.
• Treatment: Supportive, antiviral therapy is not recommended.

48. Fungal Pneumonia
• Endemic or Opportunistic fungi
• Inhalation of spores, conidia, or by the reactivation of a latent infection
• Hematogenous dissemination - immunocompromised host
• Endemic fungal pathogens (Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis,
Paracoccidioides brasiliensis, Sporothrix schenckii, Cryptococcus neoformans)
• healthy and immunocompromised persons
• Healthy persons - asymptomatic or may present with systemic signs often confused with acute bronchitis,
viral infection, mycobacterial infection, or aseptic meningitis.
• Opportunistic fungal organisms (Candida species, Aspergillus species, Mucor species) - patients with
congenital or acquired defects in the host immune defenses
• Diagnosis – difficult to prove and made on a presumptive basis
• Candida organisms and some ubiquitous filamentous fungi (Aspergillus and Scedosporium) - isolated from
oropharyngeal and respiratory tracts as colonizers
• Therapy for fungal pneumonias must include antifungal agents.

49. Conditions that may mimic ARDS

50. Acute Left-sided Heart Failure
• Complication of MI, dilated cardiomyopathy, systemic
hypertension, and both stenosis and insufficiency of the mitral
and aortic valves
• This pt – Pleuritic chest pain, no murmur or S3 gallop on
examination, hypotension, no h/o valve disease
• The combination of alveolar pulmonary edema and a
normal-sized heart is the hallmark of acute left-sided heart
failure.
• The interstitial fluid may distribute in a classical butterfly
pattern.
• Rapid improvement with diuresis and/or afterload reduction.
• Hypoxemia is usually not resistant to oxygen therapy
• Cardiac enzymes ?? (troponin and CKMB – may be unreliable
in the sepsis)
• BNP??
• EKG and Echo??
Patient with acute mitral regurgitation
because of rupture of chordae tendineae
showing the “bat-wings” appearance of a
severe alveolar type of pulmonary edema
and a normal-sized heart.
Hurst's The Heart, 14e

51. Acute on Chronic CHF
• No History of heart disease
• No S3 gallop, elevated jugular venous pulse,
peripheral edema
• No rales/wheezes
• CXR:
• Normal cardiac silhouette
• No pleural effusions
• No evidence of peribronchial thickening,
and Kerley B lines.
• Hypoxemia did not respond to the
administration of supplemental oxygen.
• Troponin??
• CKMB??
• BNP??
• EKG and Echo??
• Amount of IV fluids administered??
Hurst's The Heart, 14e

52. Diffuse Alveolar Hemorrhage
• Caused by injury or inflammation of the arterioles, venules, alveolar
wall or interstitial capillaries.
• Associated with a wide variety of disease processes
• Cytotoxic & non-cytotoxic drugs; Infection; CTD
• Cough, hemoptysis (66%), fever, and dyspnea
• In the absence of hemoptysis, new radiographic opacities (either
localized or diffuse), a falling hemoglobin level may suggest DAH
• Concomitant renal disease, specific antibodies (eg, ANCA, ANA,
ACL, AGBM), a positive culture, or positive drug screen (eg,
cocaine) may suggest or permit the diagnosis of a particular
underlying disorder.
• CT chest: Diffuse bilateral ground glass or consolidative opacities
• Sequential Broncho alveolar lavage (BAL) is a key step in the
diagnosis of DAH - Progressively more hemorrhagic lavage returns
and the presence of hemosiderin-laden macrophages on cytologic
staining - confirm the presence of alveolar hemorrhage.
Diffuse alveolar hemorrhage with bilateral pulmonary
infiltrates in a patient with rheumatic heart disease.

53. CXR: diffuse infiltrates
Elevated ESR, CRP
Renal failure: ? granulomatous
vasculitis and ? microscopic
polyangiitis
Diffuse Alveolar Hemorrhage
Often associated with autoimmune
disease (e.g vasculitis) or following
BM transplantation
No hemoptysis (1/3 of patients may
not have hemoptysis)
No evidence of manifestations of a
systemic disease (rash, myalgias,
arthralgias, or conjunctivitis)
Hematocrit trend??
Broncho-alveolar lavage showing
progressively more blood with serial
aspiration??
kidney biopsy or thoracoscopic lung
biopsy??
Favors
Against

54. Idiopathic Acute Eosinophilic Pneumonia
• Acute hypersensitivity reaction to an unidentified inhaled antigen in an
otherwise healthy individual.
• Acute febrile illness of < 4 weeks duration (< 7 days), a nonproductive
cough, and progressively worsening dyspnea; malaise, myalgias, night
sweats, and pleuritic chest pain.
• Associated with new onset or resumption of cigarette smoking; heavy
inhalational exposure to smoke, fine sand, and dust.
• Peripheral blood eosinophilia (may not be present in early phase)
• CXR: subtle reticular or ground glass opacities with Kerley B lines à
bilateral diffuse mixed ground glass and reticular opacities.
• HRCT: bilateral, random, and patchy ground-glass or reticular opacities
with small bilateral pleural effusions
• Diagnosis:
1. Acute febrile illness of short duration (one month or less)
2. Hypoxemic respiratory failure
3. Diffuse pulmonary opacities on chest radiograph
4. Bronchoalveolar lavage eosinophilia (>25 percent)
5. No evidence of infection, vasculitis, or other known precipitants
• Treatment with systemic glucocorticoids, may require mechanical
ventilation.

55. Acute or Subacute Hypersensitivity pneumonitis (HP)
• Extrinsic allergic alveolitis - immunologic reaction to an inhaled agent,
particularly an organic antigen, occurring within the pulmonary
parenchyma.
• Acute HP:
• Abrupt onset (four to six hours following exposure) of fever, chills,
malaise, nausea, cough, chest tightness, and dyspnea.
• PE: tachypnea and diffuse fine crackles.
• CXR: normal or show transient patchy, micro nodular opacities.
• Removal from exposure to the inciting antigen, leads to improvement
in symptoms and signs within 12 hours to several days and resolution
within several weeks.
• Subacute HP - gradual development of productive cough, dyspnea,
fatigue, anorexia, and weight loss; radiographic findings more extensive
• Careful exposure history, open or video-assisted thoracoscopic lung
biopsy - to make a firm diagnosis.
• Rx:
• Resolves with removal from exposure
• Systemic glucocorticoids - occasionally necessary
• Environmental controls to reduce or eliminate exposure to the
agricultural dusts, bioaerosols, and chemicals
• Advanced chronic HP - lung transplantation
Chest radiograph of a patient with pigeon breeder’s
disease with fever, dyspnea, and bibasilar rales. The
patient had kept pigeons for 5 years and presented
with fever, dyspnea, and myalgias approximately 8
hours after cleaning the pigeon coop. He had serum
antibody to pigeon dropping extract. Note bilateral
lower lobe 2- to 3-mm nodules.

56. Cryptogenic Organizing Pneumonia (COP)
• One of the Idiopathic interstitial pneumonias.
• 5th or 6th decades of life with men and women affected equally.
• Symptomatic for < 2 months and have a clinical presentation
that mimics community-acquired pneumonia.
• CXR: Multiple ground-glass or consolidative opacities.
• PFT: restrictive pattern with gas transfer defect.
• Trans bronchial biopsy or surgical lung biopsy - definitive
diagnosis of COP
• Excessive proliferation or "plugs" of granulation tissue within
alveolar ducts and alveoli, associated with chronic
inflammation in the surrounding alveoli
• Rx:
• Minimally symptomatic - monitor without therapy
• Symptomatic patients with moderate or more severe
respiratory impairment - systemic glucocorticoid therapy à
immunosuppressive agent (cyclophosphamide or
azathioprine)
Thirty-seven year old woman with a two week
history of cough, dyspnea with exertion,
fatigue, and fever. She developed respiratory
failure and was hospitalized. CXR reveals
bilateral patchy opacities and volume loss. An
open lung biopsy confirmed an extensive COP
pattern. There was complete resolution
following glucocorticoid therapy without
recurrence after glucocorticoids were
discontinued.

57. Lymphoproliferative and Hematologic Diseases Involving the Lung
Diseases Associated with Hyperplasia of Bronchus-Associated Lymphoid Tissue
Autoimmune diseases
Allergy such as asthma
Autoimmune hemolytic anemia
Celiac sprue
Hashimoto thyroiditis
Myasthenia gravis
Pernicious anemia/agammaglobulinemia
Primary biliary cirrhosis
Rheumatoid arthritis
Systemic lupus erythematosus
Sjögren syndrome
Transverse myelitis
Immunodeficiency syndromes
Common variable immunodeficiency
Unexplained childhood immunodeficiency
Virus-associated
Epstein–Barr virus
Hepatitis viruses
Human immunodeficiency virus
Drug-induced forms
Allogeneic bone marrow transplantation
Dilantin
Infections
Chlamydia
Mycoplasma
Tuberculosis
Familial

58. Lymphoproliferative and Hematologic Diseases Involving the Lung
Lymphoid Neoplasms Commonly Involving the Lungs
B-cell neoplasms
Mature B-cell neoplasms
Chronic lymphocytic leukemia/small lymphocytic lymphoma
Lymphoplasmacytic lymphoma
Plasma cell myeloma
Extraosseous plasmacytoma
Extranodal marginal zone B-cell lymphoma of mucosa-
associated lymphoid tissue (MALT-lymphoma)
Nodal marginal zone B-cell lymphoma
Follicular lymphoma
Mantle cell lymphoma
Diffuse large B-cell lymphoma
Intravascular large B-cell lymphoma
Burkitt lymphoma/leukemia
B cell proliferations of uncertain malignant potential
Lymphomatoid granulomatosis
Posttransplant lymphoproliferative disorder
T-cell and NK-cell neoplasms
Mature T-cell and NK cell neoplasms
Mycosis fungoides
Sézary syndrome
Peripheral T-cell lymphoma, unspecified
Angioimmunoblastic T-cell lymphoma
Anaplastic large cell lymphoma
Hodgkin lymphoma
Classical Hodgkin lymphoma
Nodular sclerosis classical Hodgkin lymphoma
Lymphocyte-rich classical Hodgkin lymphoma
Mixed cellularity classical Hodgkin lymphoma

59. ARDS due to
Influenza
with/without
bacterial
superinfection
1
Diffuse
Alveolar
Hemorrhage
2
Cardiogenic
Pulmonary
Edema
3

60. Information needed
History and Physical
Hemoptysis?
Sick contacts?
Pets?
Change in instruments or unusual exposure to
toxic inhalants?
Diarrhea – one-time episode?
Sore throat?
Year and Month of presentation – 2009?
Obstructive Sleep Apnea/CPAP?
How long has he been taking those
medications? Any new medication recently
started?
Allergies?
Vaccination?
History of previous renal disease? Baseline
creatinine?
Labs, Imaging & Treatment
Amount of IV fluids administered before respiratory
failure?
Vasopressors required for hypotension??
UA?
Hemoglobin and hematocrit trend?
Troponin
CKMB
BNP
HIV?
Respiratory culture - what kind of influenza? Seasonal or
H1N1?
PCR for influenza?
Sputum culture using special media for Legionella?
CT chest?
EKG and Echo?
Bronchoscopy and BAL?