Respiratory Physiology Gideon Daniel DVM

What are the LFT test you should know?

• Compliance

• Resistance

Dynamic hyperinflation and what it means to you\

Overview• DEFINITONS• SMALL AIRWAYS• EFFECT ON LUNG MECHANICS• DIAGNOSIS• THERAPY

Definitions

• Air-trapping• Intrinsic (auto) PEEP• Dynamic hyperinflation

Air-trapping/dynamic hyperinflation

Intrinsic (auto) PEEP

• Typically refers to ventilated patients

• Inadequate time for exhalation (may or may not be pathologic)

• Small airway disease/mucus

What are negative effects of autoPEEP?

• Potential for worsening cardiac pressure

• Barotrauma or hypoventilation if pressure limited ventilation

AutoPEEP• Volume limited ventilator (increasing barotrauma and mean

AWP)

35 cmH20

• Pressure limited ventilator (increasing risk of hypoventilation)

18 cmH20

Inadequate time for expiration• Inverted I: E ratio

• Short Te and fast rate

• Altered time constant

Time constant

• Lung volume changes are due to compliance of the lung and the pressure applied

• Lung volume = Compliance X ΔP• When pressure is applied to the lung, there is a time lag until

the volume change occurs• The time point at which to inflate or deflate to 63% of volume

is termed time constant• Given also by compliance X resistance

Using time constant calculation to predict air-trapping• Need to permit 4-5 time constants for complete inhalation or

exhalation• Normal lungs, ARDS, emphysema/small airway disease• Healthy dog – compliance 10 ml/cmH20; resistance 10

cmH20/L/sec• ARDS dog- compliance 3 ml/cmH20; resistance 12

cmH20/L/sec• COPD dog with air-trapping- compliance 25 ml/cmH20; 14

cmH20/L sec

Healthy• Healthy dog – compliance 10 ml/cmH20; resistance 10

cmH20/L/sec

• Time constant

• Convert ml to liter (10 ml = 0.01 L)0.01 l/cmH20 X 10 cmH20/L/sec= 0.1 secondsX 3-5 = normal inspiration/expiration should be fine in 0.3-0.5

ARDS• ARDS dog- compliance 3 ml/cmH20; resistance 12

cmH20/L/sec

• 0.003 X 12= 0.036

• X 5= 0.18 seconds

COPD• COPD dog with air-trapping- compliance 25 ml/cmH20; 14

cmH20/L sec

• 0.025 X 14 = 0.35

• X5 = 1.75 seconds

What are small airways?

• < 2 mm in diameter

• Conducting airways• Very small contribution to resistance

Small airway disease

• Asthma

• Bronchiolitis

When might we suspect air-trapping

• Clinically, we would worry with

• COPD• Ventilated animals

• * not so much ARDS

Effects of lung function

• Increased lung volume

• Increased work of breathing since operating off the ideal P-V curve

• Increase WOB leads to exhaustion and respiratory fatigue

Diagnosis

• Ventilated patients

• Spontaneous breathing patients

Ventilated

• Increasing PEEP higher than set PEEP

• Lower compliance (since at higher part of PVC curve)

• Breath-stacking at time

Spontaneous breathing

• Chest shape (barrel shaped) • Longer expiratory time/effort

• Imaging• Radiographs

• Computed tomography

Treatment

• Ventilated patients• BD• Adjust rates

• Spontaneous breathing patients• BD• Lung volume reduction

• Surgical • Bronchoscopic

Jack Cleary NOVA (arterial sample): • pH 7.329• PCO2 58• PO2 105.2• Na 147.6• K 4.94• Cl 105• Ca 1.23• BG 74• Lac 3• Crea 13.6 (BUN did not register) • TCO2 32.5• BE 4

• Characterize the Acid-base disturbance

• Is the dog on supplemental oxygen, why or why not?

• Is this acute or chronic?

Alternatives to blood gas?• Preliminary evaluation of the utility of comparing SpO2/FiO2

and PaO2/FiO2 ratios in dogs. Calabro, et al. JVECC 2013. • Numerous studies evaluated SF in people • May also be an acceptable surrogate for PaO2/FiO2 in dogs

• Partial pressure of end-tidal CO2 sampled via an intranasal catheter as a substitute for partial pressure of arterial CO2 in dogs. Pang, et al. JVECC 2007. • Dogs for sedated for intranasal catheter placement • Maybe a substitute for blood gas analysis?

Variables to consider• Effect of body position on the arterial partial pressures of

oxygen and carbon dioxide in spontaneously breathing, conscious dogs in an intensive care unit. McMillian, et al. JVECC 2009. • PaO2 was significantly higher when patients were sternal

compared to lateral recumbency • PaCO2 levels were not significantly different

What are the 5 causes of hypoxemia as outlined by WEST?

• Inadequate FiO2

• Hypoventilation

• Diffusion impairment

• Shunt

• V-Q mismatch

T or F• CO2 can diffuse about 20x as rapidly as oxygen for a given

difference in pressure. • True • Fick’s law

All of the following determine diffusion of oxygen across the respiratory membrane EXCEPT1. Membrane thickness2. Diffusion coefficient (based on solubility and molecular wt)

of the gas3. Membrane surface area4. Concentration of oxygen in the inspired air5. Partial pressure difference of gas on either side of the

membrane

What is Alveolar ventilation?• Is the rate at which new air reaches the gas exchange areas of

the lungs• During inspiration, some of the air never reaches the gas

exchange areas but instead fills respiratory passages• This air is called dead space air

• Alveolar ventilation can be increased by either (or both)• Raising tidal volume

• More effective b/c it reduces the proportions of each breath occupied by anatomic dead space

• Increasing resp frequency

ALI/ARDS• Is a syndrome of pulmonary inflammation and edema

resulting in acute respiratory failure associated with critical injury/illness

• Major difference b/w ALI and ARDS is the degree of hypoxemia as defined by the ratio of arterial oxygen tension to fractional inspired oxygen concentration (PaO2:FiO2)

Consensus in people • Clinical criteria• Acute onset of respiratory distress• Presence of bilateral pulmonary infiltrates on CXR• Pulmonary artery wedge pressure ≤ 18mmHg• No clinical evidence of left atrial hypertension

ALI vs ARDS• A PaO2/FiO2 ratio of 500 is considered normal • What ratio for ALI?• 200-300

• What ratio for ARDS?• < 200

Risk factors• Pulmonary – direct injury • Pneumonia • Contusion• Toxin • NCPE

• Extra pulmonary • Poly-trauma• Sepsis/SIRS

• Sepsis and pneumonia most common etiology

Clinical signs• May be delayed for 1-4 days• Progressive hypoxemia• Tachypnea• Respiratory distress• Cyanosis• Productive cough- actually rare

Mechanism of lung injury • Increase in endothelial permeability, allowing leakage of

protein-rich serum into the alveolar spaces • Alveolar infiltrates impaired gas exchange and decreased

lung compliance • Relatively surfactant deficiency contributes to alveolar

collapse • Inflammatory response may represent an overzealous

response on the part of both cellular and humoral immune system

Stages of lung injury • Exudative – reflects presence of protein-rich edema fluid,

hyaline membranes and wbc infiltrates

• Proliferative - As ALI/ARDS progress – proliferation of type II pneumocytes (attempts to restore the damaged epithelium)

• Fibrotic phase- as dz resolves

Cellular mechanism• Macrophages• Neutrophils • Soluble mediators • TNFa • IL-1B• TGF-B• PAF• IL 6 • CXCL-8• Eicosanoids• IL-10

• A patient breathing room air has an arterial P02 of 49mmHg, PCO2 48mmHg and respiratory exchange ratio of 0.8. What is the approximate alveolar-arterial difference for PO2 in this patient? • 41mmHg

• Is this normal or abnormal? • Abnormal; normal A-a gradient should be < 10. • Cause? Likely NOT hypoventilating –that is the the role of the A-a

gradient to exclude!• Indicates venous admixture

Which of the following is NOT considered a criteria for dx of ALI/ARDS?

1. Acute onset of respiratory distress2. Left atrial hypertension3. Decreased PaO2:FiO2 ratio4. Known risk factors (sepsis, pneumonia, etc)

Regarding ALI/ARDS, which of the following statement is true?

1. Neutrophils are generally the first effector cells of the pulmonary response

2. Coughing is frequently the first CS associated with these syndromes

3. Radiographic signs are generally more unilateral than bilateral

4. Patients with ALI have a PaO2:FiO2 ratio < 300 and those w/ ARDS have a ratio < 200mmHg

Which of the following is not a part of the consensus definition of VetALI/VetARDS?

1. Acute onset (< 24hrs) of tachypnea and labored breathing2. Known risk factors are SIRS, near-drowning, smoke

inhalation 3. Evidence of pulmonary capillary leak without increased

pulmonary capillary pressure 4. Evidence of inefficient gas exchange 5. Evidence of diffuse pulmonary inflammation

Which of the following describes the proliferative phase of ALI/ARDS?

1. Organization of exudates and development of fibrosis with increasing numbers of Type II pneumocytes

2. Collagen deposition in the alveolar, vascular and interstitial beds with development of microcysts in the pulmonary parenchyma

3. Pulmonary vascular leakage and inflammatory cell infiltration with loss of capillary integrity, alveolar epithelial damage, accumulation of protein-rich fluid and development of pulmonary edema

Which of the following statements is false?1. The exudative phase is the first phase of ALI/ARDS, and is

characterized by pulmonary vascular leakage and inflammatory cell infiltration

2. During the exudative phase, type II pneumoncytes are replaced with type I pneumoncytes

3. The proliferative phase is the 2nd phase of ALI/ARDS, and is characterized by proliferation of type II pneumoncytes

4. The fibrotic phase of ALI/ARDS involves collagen deposition in the alveolar, vascular and interstitial beds

Which of the following does NOT occur in the proliferative phase of ALI/ARDS?

1. Collapse of alveoli2. Development of microcysts in pulmonary parenchyma3. Alerted function of type II pneumocytes4. Pulmonary hypertension5. Fibrin filled alveoli

All are pathologic changes associated with ALI/ARDS EXCEPT?1. Ventilation-perfusion mismatch 2. Decreased compliance3. Increased intra-pulmonary shunt 4. Decreased dead space relative to tidal volume

Which of the following does NOT act as a pro-inflammatory mediator in the pathogenesis of ALI/ARDS?1. IL-62. TNF-alpha3. IL-104. PAF5. TGF-beta

All of the following are known risk factors of developing ALI/ARDS except?

1. Pancreatitis2. GDV3. Sepsis4. L CHF5. DIC

What is another role of platelet activating factor (PAF) other than activation of platelets?

1. Signals the release of pro-inflammatory cytokines2. Causes vasodilation and bronchoconstriction3. Impairs the vascular endothelial effects of neutrophils4. Decreases development of lung injury 5. Promotes neutrophil migration

Which mediators plays a major role in neutrophils recruitment and activation?

1. PAF2. TNF alpha3. TGF beta4. IL1b

What would be the typical BAL result from a dog with ALI/ARDS?

1. Proteinaceous background, neutrophils2. Pyogranulomatous effusion3. Suppurative and septic4. Lymphoplasmacytic

Which of the following is a key mediator in tissue fibrosis during the late stages of ALI/ARDS?1. PAF 2. Alveolar macrophages3. TGF-beta4. IL-6

Which eicosanoids are suspected to be the major players in the pathogenesis of ALI/ARDS?1. Prostaglandins 2. Prostacyclins3. TXA24. Leukotrienes 5. 1 and 3

Matching- Which receptors? • Responsible for bronchodilator?• B2

• Responsible for bronchoconstriction?• Muscarinic

Matching Definitions

Matching Definitions

T or F• In health, the greatest resistance to airflow occurs in small

terminal bronchioles• False

The most important factor limiting flow rate during most of a forced expiration from total lung capacity is:1. Rate of contraction of expiratory muscles2. Action of diaphragm3. Constriction of bronchial smooth muscle 4. Elasticity of chest wall 5. Compression of airways

What is the difference b/w anatomic and physiologic dead space?

1. Anatomic dead space: represents the volume of conducting airways

2. Physiologic dead space: the part of the tidal volume which does not participate in gas exchange

Which of the following are components of the conducting airways?1. Trachea, bronchioles, alveolar ducts, and bronchi2. Bronchi, resp bronchioles and alveolar sacs3. Bronchi, bronchioles, terminal bronchioles and respiratory

bronchioles 4. Trachea, bronchi, bronchioles, and terminal bronchioles

Which of the following is NOT true about surfactant?

1. Surfactant decreases alveolar surface tension2. Surfactant is secreted primarily by type I pneumocytes as

well as goblet cells 3. Surfactant is spread over the alveolar surface and reduces

the surface tension to 1/12 to ½ of the surface tension of a pure water surface

4. As an alveolus becomes smaller, the surfactant molecules on the alveolar surface are squeezed together, increasing their concentration

Which of the following statements is FALSE? Pulmonary surfactant:

1. Reduces the surface tension of the alveolar lining liquid2. Is secreted by type II alveolar epithelial cells 3. Contains dipalmitoyl phosphatidylcholine4. Increases the work required to expand the lung5. Helps to prevent transudation of fluid from the capillaries

into the alveolar spaces

References/Additional reading• Preliminary evaluation of the utility of comparing SpO2/FiO2 and PaO2/FiO2 ratios in

dogs. Calabro, et al. JVECC 2013.• Partial pressure of end-tidal CO2 sampled via an intranasal catheter as a substitute for

partial pressure of arterial CO2 in dogs. Pang, et al. JVECC 2007. • Effect of body position on the arterial partial pressures of oxygen and carbon dioxide

in spontaneously breathing, conscious dogs in an intensive care unit. McMillian, et al. JVECC 2009.

• Evaluation of respiratory parameters at presentation as clinical indicators of the respiratory localization in dogs and cats with respiratory distress. Sigrist, et al. JVECC 2011.

• Acute lung injury and acute respiratory distress syndromes in veterinary medicine: consensus definitions: the Dorothy Russell Havemeyer Working Group on ALI and ARDS in Veterinary Medicine. Wilkins, et al JVECC 2007.

• Acute respiratory distress syndrome in dogs and cats: a review of clinical findings and pathophysiology. DeClue, et al. JVECC 2007.

• Acute lung injury and Acute respiratory distress syndrome. Carpenter, et al Compendium 2001.

• Respiratory physiology 8th edition. West Ch 3-6. • Textbook of respiratory disease in dogs and cats. King Ch 68, 23, 24.

• Airway physiology and clinical function testing. Hoffman. Vet Clinics 2007• Small animal critical care medicine. Silverstein, Hopper, 1st edition.

Chapters 34, 15. • Ettinger and Feldman. “Textbook of veterinary internal medicine, 7th

edition, Chapter 143, 124, 73. • A case-based review of a simplified quantitative approach to acid-base

analysis. Hopper, Haskins. JVECC 2008. • Pulmonary abnormalities in dogs with renal azotemia. Boedec et al. JVIM

2012. • Indications for and outcome of positive-pressure ventilation in cats: 53

cases (1993-2002). Lee, et al. JAVMA 2005. • Comparison of two fluid-management strategies in acute lung injury.

Weidemann, et al. NEJM 2006. • Comparison of the SPO2/FIO2 ratio and the PAO2/FIO2 ratio in patients

with acute lung injury or ARDS. Rice, et al Chest 2007.