Respiratory System pathology

1. Acute Respiratory Distress
Syndrome (ARDS)
Dr. Prasad Gaikwad
Guide- Dr. R.S.Khot
Dept of internal Medicine
IGGMC, Nagpur

2. ARDS
• Definition
• Etiology
• Clinical course and Pathophysiology
• Clinical features
• Differential diagnosis
• Diagnosis
• Treatment
• Newer modalities- evidence based medicine

3. • 1st described 1967 (Ashbaugh et al)
• Incidence 1.5 -7.5/ 100000 population
• 28 day mortality 25 – 44%1

4. Other names
• Adult hyaline-membrane disease
• Adult respiratory insufficiency syndrome
• High output respiratory failure
• Congestive atelectasis
• Hemorrhagic lung syndrome
• Stiff-lung syndrome
• Shock lung
• White lung

5. Definition
• Clinical syndrome of severe dyspnoea of rapid onset,
hypoxemia and diffuse pulmonary infiltrates with
absence of left atrial hypertension leading to
respiratory failure.
• ALI is less severe form but may evolve into ARDS
• ALI Po2/Fio2 ratio <300 mmHg.
• ARDS Po2/Fio2 ratio <200 mmHg.

6. • Berlin definition of ARDS

7. Clinical disorders associated with ARDS
Direct lung injury
1)pneumonia
2)aspiration of gastric contents
3)pulmonary contusion
4)near drowning
5)toxic inhalation injury
Indirect lung injury
1) Sepsis
2)Severe trauma
3)Multiple fractures
4) Multiple blood transfusion
5)Pancreatitis
6) Cardiopulmonary bypass

8. Clinical course and Pathophysiology
• 3 phases
1)Exudative phase- hyaline membrane- 0 to 7 day
2) Proliferative phase- interstitial inflammation- 7 to 21 day
3) Fibrotic phase- fibrosis- after 21 days

9. Pathophysiology
during exudative
phase
Direct or indirect injury to the
alveolus causes alveolar
macrophages to release pro-
inflammatory cytokines
↓
Cytokines attract neutrophils
into the alveolus and
interstitum, where they damage
the alveolar-capillary
membrane (ACM).
↓
. ACM integrity is lost,
interstitial and alveolus fills with
proteinaceous fluid, surfactant
can no longer support alveolus

10. • Exudative Phase
• Neutrophilic Infiltrate
• Alveolar Haemorrhage
• Proteinaceous Pulmonary Oedema
• Cytokines (TNF, IL1,8)
» ↑ Inflammation
» ↑ Oxidative Stress and Protease Activity
» ↓ Surfactant Activity
» Atelectasis
Elastase- induced capillary and alveolar damage3
↑ Alveolar flooding
↓ Fluid clearance

11. Proliferative phase
lasts around 7-21 days
initiation of lung repair
organisation of alveolar exudates
shift from PMN to lymphocyte rich infiltrate
Type II pneumocyte
Synthesize surfactant
proliferate
differentiate into Type I cells
reline alveolar walls
Fibroblast proliferation
interstitial/alveolar fibrosis

12. Fibrotic phase
Extensive alveolar duct and interstitial fibrosis.
Emphysema like changes with bullae formation.
Fibrosis may result into progressive vascular occlusion and
pulmonary hypertension.

13. Consequences of lung injury include:
1)Impaired gas exchange-due to hyaline membrane
V/Q mismatch
Related to filling of alveoli
Shunting causes hypoxemia
Increased dead space
Related to capillary dead space and V/Q mismatch
Impairs carbon dioxide elimination
Results in high minute ventilation
2)Decreased compliance- more in dependent lung portions
Hallmark of ARDS
Consequence of the stiffness of poorly or nonaerated lung
Fluid filled lung becomes stiff/boggy
Requires increased pressure to deliver Vt

14. 3) Increased pulmonary arterial pressure
Occurs in up to 25% of ARDS patients
Results from hypoxic vasoconstriction
Positive airway pressure causing vascular compression
Can result in right ventricular failure

15. Clinical features
Symptoms
• Acute onset exertional dyspnoea leading to dyspnoea at rest.
• Tachypnea
• Anxiety
• Agitation
• Increased work of breathing
Physical examination
• Tachypnea
• Tachycardia
• Increased FiO2 to maintain saturation
• May be febrile of hypothermic
• Cold extremities
• Bilateral crepitation
• Manifestation of underlying cause
• Cardiogenic pulmonary edema to be ruled out

16. Differential diagnosis
• Cardiogenic pulmonary edema
• Diffuse pneumonia
• Alveolar hemorrhage
• Acute interstitial pneumonitis
• Hypersensitive pneumonitis
• Neurogenic pulmonary edema

17. Diagnosis
Mainly clinical-no specific diagnostic tests
Laboratory tests
Diagnostic imaging
Hemodynamic monitoring
Bronchoscopy

18. Lab tests
• ABG analysis
PaO2/FIO2 ratio is less than 200.
Respiratory acidosis later on metabolic acidosis
• To exclude cardiogenic pulmonary edema-
B-type natriuretic peptide (BNP) value <100 pg/mL
Echocardiogram
• Hematological- either leukocytosis or leucopenia
• Renal- (ATN) often ensues in the course of ARDS
• Hepatic-Liver function abnormalities may be noted in either a
pattern of hepatocellular injury

19. ABG in ARDS
Initial stages
PaO2 < 60 mmHg
PaCO2 < 35 mmHg
pH- may normal or increased showing respiratory alkalosis
P/F ratio <200
Late stages
PaO2 more falling despite oxygen therapy
PaCO2 >45 mmHg showing respiratory acidosis
Serum bicarbonates < 22 mEq/L showing metabolic acidosis
P/F ratio <200

20. Radiological –chest x-ray
Shows bilateral alveolar
and interstitial opacities
involving atleast three-
quarters of lung fields.
Difficult to d/w from
cardiogenic pulmonary
edema.

21. Initial patchy peripheral
distribution but later on
progresses to ground glass
alveolar opacities.

22. Radiological CT thorax
heterogeneity
of alveolar
involvement is
apparent on CT
scan

23. Invasive Hemodynamic Monitoring
• Hemodynamic monitoring with a pulmonary artery (Swan-
Ganz) catheter may be helpful in selected cases for
distinguishing cardiogenic from noncardiogenic pulmonary
edema.
• This allows measurement of RA pressure, RV pressure, PA
pressure and pulmonary artery occlusion pressure (PAOP).
• A PAOP lower than 18 mm Hg is usually consistent with
noncardiogenic pulmonary edema.
• However their use is controversial.
• One large retrospective cohort study of ICU showed that
patients with pulmonary artery catheters had an increased
mortality rate, hospital cost, and length of stay.
• Hence not indicated for routine patients.

24. Bronchoscopy
• May be considered to evaluate the possibility of infection,
alveolar hemorrhage, or acute eosinophilic pneumonia in
patients acutely ill with bilateral pulmonary infiltrates
• >10000 organisms/mL is significant for diagnosis of ARDS for
patients who are not treated with antibiotics.
• Presence of neutrophils in the BAL fluid with the presence of
intracellular organisms is helpful in diagnosis of ARDS
• Analysis of the types of cells present in the BAL fluid may be
helpful in the differential diagnosis of patients with ARDS.
>20% eosinophils-acute eosinophilic pneumonia
high proportion of lymphocytes may be observed in
acute hypersensitivity pneumonitis, sarcoidosis, or bronchiolitis
obliterans-organizing pneumonia (BOOP)

25. Management of ARDS
• Treat the underlying cause.
• Conservative fluid management.
• Non invasive ventilation.
• Mechanical ventilation.
• Other modalities.

26. Treating underlying cause
The underlying cause may be treated with broad
spectrum antibiotic as with patients having
pneumonia, pancreatitis and severe sepsis
Surgical intervention if needed should be carried
out

27. Fluid management
• Aggressive attempts to reduce left atrial filling pressure-will
help in minimizing pulmonary edema and improved arterial
oxygenation
• Can be achieved by fluid restriction and diuresis
• Approach limited by
hypotension
Hypoperfusion of end organs
Secondary ARDS due to remote infection and
inflammation

28. Non-invasive ventilation
• Continuous CPAP or Non invasive ventilation using BiPAP mask
may be beneficial in early course of disease.
• But often patients unable to maintain saturation , get drowsy,
develop altered sensorium
• Very little data available for its use
• Invasive mechanical ventilation is mandatory

29. Mechanical ventilation
• Goals of mechanical ventilation
Low tidal volume ventilation to avoid volutrauma
Maintain O2 saturation between 85-90%
Minimizing FiO2 < 0.65 within first 48 hrs of ventilation
Optimum PEEP
Minimal plateau pressures

30. Mechanical ventilation
Low Tidal Volume Ventilation
• ONLY RECOMMENDED BEST THERAPEUTIC APPROACH OVER 4
DECADES
• When compared to larger tidal volumes, Vt of 6ml/kg of ideal body
weight:
• Decreased mortality
• Increased number of ventilator free days
• Decreased extrapulmonary organ failure
• Mortality is decreased in the low tidal volume group despite these
patients having:
• Worse oxygenation
• Increased pCO2 (permissive hypercapnia)
• Lower pH

31. • ARDS affects the lung in a heterogeneous fashion
• Normal alveoli- can cope up with normal or higher vt
• Injured alveoli -can potentially participate in gas exchange,
susceptible to damage from opening and closing of higher
vt
• Damaged alveoli-filled with fluid, do not participate in gas
exchange
• High tidal volumes
• Overdistention of alveoli
• Local inflammatory response resulting in systemic
inflammation with release of inflammatory cytokines
• Recommended 4-6ml/kg

32. Optimum PEEP
• Empirically set to a level that it will minimize FiO2 and
maximize PaO2.
• On most modern mechanical ventilators it is possible to set
static pressure –volume curves.
• Titration of PEEP to the lower inflection point on pressure –
volume curve- keeps lungs open, improves oxygenation,
minimizes barotrauma.
• Optimum PEEP for most of patients ranges from 12-15 mmHg

33. PEEP

34. Inverse ratio ventilation
I:E ratio > 1:1
Inspiratory time lengthened and expiratory time shortened.
Same strategy like increasing ventilator prescribed PEEP
May help to keep FiO2 < 0.6 to avoid oxygen induced toxicity
Long term survival benefit is questionable.

35. Airway Pressures in ARDS
• Plateau pressure is most predictive of lung injury
• Goal- plateau pressure < 30, the lower plateau pressure the
better is outcome
• Decreases alveolar over-distention and reduces risk of lung
strain
• Adjust tidal volume to ensure plateau pressure at goal
• It may be permissible to have plateau pressure > 30 in some
cases
• Obesity
• Pregnancy
• Ascites

36. • Assess cause of high Plateau Pressures
• Always represents some pathology:
– heart failure
– Pneumothorax
– Auto-peeping
– Mucus Plug
– Right main stem intubation
– Chest wall fat / Obesity

37. Permissive hypercapnia
• It’s a consequence of low Vt ventilation.
• Patients often develop hypercapnia and respiratory acidosis.
• Small studies in favour of PaCO2 levels as high as 375mmHg
and pH as low as 6.6
• However recent meta-analysis suggest that PaCO2 of 60-70
mmHg and pH range 7.2-7.25 are sufficient to avoid
volutrauma.
• Troublesome part- patients often develop hyperventilation
and ventilator asynchrony; needs managed with
neuromuscular blockade.

38. Ventilatory parameters
First stage
1)Calculate patient’s predicted body weight:
• Men (kg) = 50 + 2.3(height in inches – 60)
• Females (kg) = 45.5 + 2.3(height in inches – 60)
2)Set Vt = predicted body weight x 8 mL/kg
3)Add PEEP of 5-7 cm H2O
4)Reduce Vt every 2hrs by 1 mL/kg till 6mL/kg PBW
Second stage
Now set target plateau pressure <30 cmH2O by adjusting Vt till
4mL/kg
Third stage
1)Target pH= 7.30-7.45
2)If pH <7.30 then adjust RR till 35br per minute

39. Weaning
• Daily CPAP breathing trial
– FiO2 <.40 and PEEP <8
– Patient has acceptable spontaneous breathing efforts
– No vasopressor requirements,
• Pressure support weaning
– PEEP 5, PS at 5cm H2O if RR <25
– If not tolerated, ↑RR, ↓Vt – return to A/C
• Unassisted breathing
– T-piece, trach collar
– Assess for 30minutes-2 hours

40. Weaning
• Tolerating Breathing Trial?
– SpO2 ≥90
– Spontaneous Vt ≥4ml/kg PBW
– RR ≤35
– pH ≥7.3
– Pass Spontaneous Awakening Trial (SAT)
– No Respiratory Distress ( 2 or more)
• HR < 120% baseline
• No Accessory muscle use
• No Abdominal Paradox
• No Diaphoresis
• No Marked Dyspnea
– If tolerated, consider extubation

41. Other modalities
• Prone position ventilation
• High frequency ventilation
• Partial liquid ventilation
• Extracorporeal membrane oxygenation(ECMO)
• Systemic glucocorticoids
• Surfactant replacement
• Inhaled nitric oxide

42. • Prone position ventilation
• Redistribution of blood & ventilation to least affected
areas of lung
• Secretion clearance
• Shifts mediastinum anteriorly – assists recruitment of
atelectatic areas
• ? reduce lung injury
• Reduced lung compression by abdominal contents

43. Hypothesis: Early application of prone positioning would
improve survival in patients with severe ARDS.
Conclusion: Early application of prolonged prone positioning
significantly decreased 28 day and 90 mortality in patients with
severe ARDS.

44. • High frequency oscillation ventilation(HFOV)
uses small tidal volumes(1-2 mL/kg) at a very fast rate(5-20
cycles per second)
Had been useful in animal studies
Lack proven benefit in human. Instead hazardous

45. -Randomized control trial, stopped with 548 of 1200 patients
-Found early initiation of HFOV does not reduce hospital mortality and
may increase hospital mortality

46. • Extracorporeal membrane oxygenation(ECMO)
had proven benefit for neonatal respiratory syndrome but
not for ARDS
• Partial liquid ventilation
uses high density , inert liquid of per-fluorocarbon which
solubilizes oxygen and carbon dioxide; thought to improve
oxygenation.
No clear benefit on survival

47. Inhaled nitric oxide
can be of help in early course of treatment to improve
oxygenation but no improved survival benefit
Glucocorticoids
To suppress inflammation in early ARDS did not have any
have any evidence based recommendation
Instead deleterious effect on pulmonary inflammation

48. • Enrolled 282 patients with aerosolized albuterol and saline
placebo with primary outcome as ventilator free days.
• Conclusion -aerosolized albuterol does not improve clinical
outcomes in patients with ALI. Routine use of b2-agonist
therapy in mechanically ventilated patients with ALI can not
be recommended

49. Evidence –based recommendations for ARDS
therapies
Treatment Recommendation
Low tidal volume A
Minimize left atrial filling
pressure
B
High PEEP C
Prone position C
ECMO C
High frequency ventilation D
glucocorticoids D
Surfactant replacement
and inhaled nitric oxide
D
A- recommended on
evidence based RCTs
B- recommended based on
supportive but limited
clinical trials
C- recommended only as
alternative therapy
D- not recommended as
evidence is against efficacy

50. Prognosis
• Mortality ranges from 26-44%
• Mostly attributable to underlying cause of ARDS
• Age is most important predictor of mortality
• Other predictors- presence of liver damage, alcohol abuse,
APACHE III score, presence of kidney injury
• Patients >60yrs have threefold mortality than <60yrs
• Patients having direct lung injury have twofold more mortality
than indirect lung injury.

51. Sequelae
• Patients usually recover complete lung functions within 6
months.
• One third of Survivors have normal spirometry and diffusion
capacities after 6 months.
• Significant rates of depression and post traumatic stress
disorder amongst survivors.

52. Thank you