7Intrinsic (auto) PEEP Typically refers to ventilated patients Inadequate time for exhalation (may or may not be pathologic)Small airway disease/mucus
8What are negative effects of autoPEEP? Potential for worsening cardiac pressureBarotrauma or hypoventilation if pressure limited ventilation
9AutoPEEPVolume limited ventilator (increasing barotrauma and mean AWP)35 cmH20
10Pressure limited ventilator (increasing risk of hypoventilation) 18 cmH20
11Inadequate time for expiration Inverted I: E ratioShort Te and fast rateAltered time constant
12Time constantLung volume changes are due to compliance of the lung and the pressure appliedLung volume = Compliance X ΔPWhen pressure is applied to the lung, there is a time lag until the volume change occursThe time point at which to inflate or deflate to 63% of volume is termed time constantGiven also by compliance X resistance
13Using time constant calculation to predict air-trapping Need to permit 4-5 time constants for complete inhalation or exhalationNormal lungs, ARDS, emphysema/small airway diseaseHealthy dog – compliance 10 ml/cmH20; resistance 10 cmH20/L/secARDS dog- compliance 3 ml/cmH20; resistance 12 cmH20/L/secCOPD dog with air-trapping- compliance 25 ml/cmH20; 14 cmH20/L sec
14HealthyHealthy dog – compliance 10 ml/cmH20; resistance 10 cmH20/L/secTime constantConvert 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
27Jack Cleary NOVA (arterial sample): pH 7.329 PCO2 58 PO2 105.2 Na 147.6K 4.94Cl 105Ca 1.23BG 74Lac 3Crea 13.6 (BUN did not register)TCO2 32.5BE 4Characterize the Acid-base disturbanceIs the dog on supplemental oxygen, why or why not?Is this acute or chronic?Primary respiratory acidosis and metabolic alkalosis (as expected compensation in the acute setting is around 26.7 not 32.5)- HCO3 increase 0.15meq/L for every 1mmhg increase in PCO2 (vs 0.35 w/ chronic). If chronic would be a simple disorder- i.e respiratory acidosis with metabolic compensation.On supp oxygenAcute
28Alternatives 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 peopleMay also be an acceptable surrogate for PaO2/FiO2 in dogsPartial 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 placementMaybe a substitute for blood gas analysis?Excluded dogs with SPO2 < 80, > 97. Showed that SF and PF in dogs spontaneously breathing room air had good correlation. Median SF was 435 and PF 334. Enrolled 38 dogs.SF < 315 corresponded w/ PF < 300 and SF < 235 corresponded w/ PF 200.Threshold of 315 was 91% Se and 56% Sp for ALI and threshold of 235 was 85% Se and 85% Sp for ARDS----In non-panting healthy dogs, as w/ previous study.
29Variables to considerEffect 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 recumbencyPaCO2 levels were not significantly different
30What are the 5 causes of hypoxemia as outlined by WEST?
32T or FCO2 can diffuse about 20x as rapidly as oxygen for a given difference in pressure.TrueFick’s lawFick’s law: the rate of transfer of gas through a sheet of tissue is proportional to tissue area and difference in partial pressures b/w the two sides, and inversely related to the tissue thickness. In the lungs the tissue area is large (50-100m2) and thickness is small (0.3um). Rate of transfer is proportional to diffusion constant (D) which depends on properties of tissue and gas.
33All of the following determine diffusion of oxygen across the respiratory membrane EXCEPT Membrane thicknessDiffusion coefficient (based on solubility and molecular wt) of the gasMembrane surface areaConcentration of oxygen in the inspired airPartial pressure difference of gas on either side of the membrane4
34What is Alveolar ventilation? Is the rate at which new air reaches the gas exchange areas of the lungsDuring inspiration, some of the air never reaches the gas exchange areas but instead fills respiratory passagesThis air is called dead space airAlveolar ventilation can be increased by either (or both)Raising tidal volumeMore effective b/c it reduces the proportions of each breath occupied by anatomic dead spaceIncreasing resp frequency
35ALI/ARDSIs a syndrome of pulmonary inflammation and edema resulting in acute respiratory failure associated with critical injury/illnessMajor 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)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)
36Consensus in people Clinical criteria Acute onset of respiratory distressPresence of bilateral pulmonary infiltrates on CXRPulmonary artery wedge pressure ≤ 18mmHgNo clinical evidence of left atrial hypertension
37ALI vs ARDS A PaO2/FiO2 ratio of 500 is considered normal What ratio for ALI?What ratio for ARDS?< 200
38Risk factors Pulmonary – direct injury Extra pulmonary PneumoniaContusionToxinNCPEExtra pulmonaryPoly-traumaSepsis/SIRSSepsis and pneumonia most common etiologyCommon sequeal of bacterial pneumonia, aspiration pneumonia, sepsis or shock. Although specfici criteria has not been identified in cats, severe sepsis has been associated w/ necropsy findings consistent with ALI/ARDS
39Clinical signs May be delayed for 1-4 days Progressive hypoxemia TachypneaRespiratory distressCyanosisProductive cough- actually rareMay be delayed for 1-4 days after the inciting event triggers the pulmonary infalmmatory responsePE: harsh lung sounds, progressing to crackles, orthopena, utilization of auxiliary resp muscles and foamy pink expectorate in severe cases.
40Mechanism of lung injury Increase in endothelial permeability, allowing leakage of protein-rich serum into the alveolar spacesAlveolar infiltrates impaired gas exchange and decreased lung complianceRelatively surfactant deficiency contributes to alveolar collapseInflammatory response may represent an overzealous response on the part of both cellular and humoral immune systemMR as high as 40-60% in humans (animals surviving rare)- most die w/in first 2wks following diagnosis.For patients that have recvoery or resolution of their pulmonary lesions, there is complete or nearly complete recovery of pulmonary fnc and QOL
41Stages of lung injuryExudative – reflects presence of protein-rich edema fluid, hyaline membranes and wbc infiltratesProliferative - As ALI/ARDS progress – proliferation of type II pneumocytes (attempts to restore the damaged epithelium)Fibrotic phase- as dz resolvesExudative phase- pul vacular leakage and inflammatory cell infiltration; loss of capillary integrity, alveolar epithelial damage, accumulation of protien-rich fluid and dev of pulmonary edema are char feactures; Lung architecture beocmes altered as type I alveolar pneumocyte which are responsible for gas exchange are irrversibly damaged; b/c type I are unable to replicate, type II abandan their normal fnc of surfactant production to repair the denuded areas. -- type I death and alterred II fnc leads to formation of hylanine membranes, def of surfactant and collapse of alveoli;Proliferative phase- organization of exudate and dev of fibrosis char the proliferative phase; Type II proliferates in an effort to repair the denuded epithelial surfaces; Fibroblastic proliferation, initally in the pulmoanry interstitium and later in the alveolar lumen, lead to narrowing and collapse of the airspaces and pulmonary hypertension.Fibrotic- clinical manifestations of fibrosis are considered a late stage of ALI/ARDS, initiation of fibrosis actually begins much earlier in the syndrome. Magnitude- variable- from minimal to severe. Involves collagen deposition in the alveolar, vascular and intersitital beds. In humans, fibrosis is a key predictor of survival. Experimentally, can occur w/in 40d after induction of lung injury in dogs.
42Cellular mechanism Macrophages Neutrophils Soluble mediators TNFa IL-1BTGF-BPAFIL 6CXCL-8EicosanoidsIL-10macropahges- are the earliest effector cells of the pulmonary inflammatory response – produce cytokines and chemokines include TNFa, IL1B and ROS. Activation and elaboration of proinflammatory mediators to promote neutrophil migration and directly injure alveolar epithelial cells through induction of apoptosisNeutrophils: accumulate in the early stage and predominate in the BAL fluid. Release mediators that leads to dysfunction and death of alveolar epithelial cells and decreased surfactant production. Exact role is not completely understood. DO they help macrophage initiate ALI/ARDS are simply responding to commands from macrophage?TNFa and IL-1B- predominantly form activated macrophages. Trigger additional production of inflammatory mediators- play essential role in neutrophil recruitment and activation. IL-1B also stimulates inflammatory and fibroproliferative processes. TNFa and IL1B are the earliest soluble mediators in ALI/ARDS with increased concentrations 30-90min post injury. There is sign higher concentrations of both mediators in dogs w/ ALI/ARDS form direct injury vs systemic injuryTGFB- key mediator of tissue fibrosis, can be produced by every cell type. Promotes fibroproliferative response during latter phase of ALI/ARDS. Although late-stage mediator, expression is markedly increased as early as 2d after induction of injury. So likely has other roles, such as promoting pulmonary edema during the exudative phase. Also a chemoattract for macrophage/No and stimulates macrophage production of TNFa, IL-1B and PAFPAF: macrophage, No and EC produce PAF. In addition to activating plts, PAF is a potent pro-inflammatory mediator that acts also as a VD and BC. Much of the vascular endothelial effects of No are mediated through secretion of PAF.IL5- a wide range of cells can produce IL5. Induces syn of APP; excellent predictor of ALI/ARDS severity in human patients with conditions such as spesis and pancreatitis. Critical mediator of fiborblast activation and proliferation and likely plays a role in the fibroproliferative phase.CXCL8 (IL8)- derived from many cells; stimulates No recruitment and activates neutrophils, causing granule and leukotriene release and stimulates the resp burst. Severity of pulmonary neutrophila and mortality in human ALI/ARDS seem to correlate w/ CXCL-8.Eicosanoids- grp of hormones produced from arachadonic acid that include PG, TX and LK.IL10- anti-inflammatory- in humans with ~ risk factors, those who develop ALI/ARDS have lower circulating conc of IL10 and in additional, corresponds w/ poor outcome.In general immunomodulation is tricky as some mediations (like IL1-B and COX2) are initially proinflammatory mediators but then promote repair in later stages.
43Is this normal or abnormal? 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?41mmHgIs 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 admixturePI x 0.21 = 150mmhgPAO2 = PIO2 – PaCo2/ R 150 – 60 90A-a: 41
44Which of the following is NOT considered a criteria for dx of ALI/ARDS? Acute onset of respiratory distressLeft atrial hypertensionDecreased PaO2:FiO2 ratioKnown risk factors (sepsis, pneumonia, etc)2
45Regarding ALI/ARDS, which of the following statement is true? Neutrophils are generally the first effector cells of the pulmonary responseCoughing is frequently the first CS associated with these syndromesRadiographic signs are generally more unilateral than bilateralPatients with ALI have a PaO2:FiO2 ratio < 300 and those w/ ARDS have a ratio < 200mmHg4
46Which of the following is not a part of the consensus definition of VetALI/VetARDS? Acute onset (< 24hrs) of tachypnea and labored breathingKnown risk factors are SIRS, near-drowning, smoke inhalationEvidence of pulmonary capillary leak without increased pulmonary capillary pressureEvidence of inefficient gas exchangeEvidence of diffuse pulmonary inflammationActually 72hrs3) i.e bilateral/diffuse infiltrates4) Hypoexima w/o PEEP i.e ≤300 or 2005) BAL- neutrophila
47Which of the following describes the proliferative phase of ALI/ARDS? Organization of exudates and development of fibrosis with increasing numbers of Type II pneumocytesCollagen deposition in the alveolar, vascular and interstitial beds with development of microcysts in the pulmonary parenchymaPulmonary vascular leakage and inflammatory cell infiltration with loss of capillary integrity, alveolar epithelial damage, accumulation of protein-rich fluid and development of pulmonary edema12) Fibrotic3) Exudative phase
48Which of the following statements is false? The exudative phase is the first phase of ALI/ARDS, and is characterized by pulmonary vascular leakage and inflammatory cell infiltrationDuring the exudative phase, type II pneumoncytes are replaced with type I pneumoncytesThe proliferative phase is the 2nd phase of ALI/ARDS, and is characterized by proliferation of type II pneumoncytesThe fibrotic phase of ALI/ARDS involves collagen deposition in the alveolar, vascular and interstitial beds2) Type I is replaced with type II
49Which of the following does NOT occur in the proliferative phase of ALI/ARDS? Collapse of alveoliDevelopment of microcysts in pulmonary parenchymaAlerted function of type II pneumocytesPulmonary hypertensionFibrin filled alveoli2- this occurs in fibrotic phase
50All are pathologic changes associated with ALI/ARDS EXCEPT? Ventilation-perfusion mismatchDecreased complianceIncreased intra-pulmonary shuntDecreased dead space relative to tidal volume4
51Which of the following does NOT act as a pro-inflammatory mediator in the pathogenesis of ALI/ARDS? IL-6TNF-alphaIL-10PAFTGF-betaIL10
52All of the following are known risk factors of developing ALI/ARDS except? PancreatitisGDVSepsisL CHFDIC4
53What is another role of platelet activating factor (PAF) other than activation of platelets? Signals the release of pro-inflammatory cytokinesCauses vasodilation and bronchoconstrictionImpairs the vascular endothelial effects of neutrophilsDecreases development of lung injuryPromotes neutrophil migration2
54Which mediators plays a major role in neutrophils recruitment and activation? PAFTNF alphaTGF betaIL1b2 and 4
55What would be the typical BAL result from a dog with ALI/ARDS? Proteinaceous background, neutrophilsPyogranulomatous effusionSuppurative and septicLymphoplasmacytic1
56Which of the following is a key mediator in tissue fibrosis during the late stages of ALI/ARDS? PAFAlveolar macrophagesTGF-betaIL-63
57Which eicosanoids are suspected to be the major players in the pathogenesis of ALI/ARDS? ProstaglandinsProstacyclinsTXA2Leukotrienes1 and 35
58Matching- Which receptors? Responsible for bronchodilator?B2Responsible for bronchoconstriction?Muscarinic
59Matching DefinitionsTwo major lung volume categories- dynamic and static. Dynamic- tidal volume, inspiratory and expiratory reserve volume and vital capacity; Static- functional residual capacity and residual volumeInspiratory reserve volume: the maximum extra volume of air that can be inspired over and above the normal tidal volumeMaximum voluntary expirationExpiratory reserve volume: the maximum extra volume of air that can be expired by forceful expiration after the end of a normal tidal expirationResidual volume: the volume of air remaining in the lungs after the most foreceful expirationVital capacity: inspiratory resrve volume + tidal volume + expiratory reserve volume; the max amt of air a person can expel from the lugs after first filling the lungs to their maximum extent and then expiring to the maximum extentFunctional residual capacity: expiratory reserve volume + residual volume; the amt of air that remains in the lungs at the end of normal expirationTotal lung capacity: vital capacity + residual volume; maximum volume to which the lungs can be expanded with the greatest possible effortTidal volume: the volume of air inspired or expired with each normal breath
60Matching DefinitionsTwo major lung volume categories- dynamic and static. Dynamic- tidal volume, inspiratory and expiratory reserve volume and vital capacity; Static- functional residual capacity and residual volumeInspiratory reserve volume: the maximum extra volume of air that can be inspired over and above the normal tidal volumeMaximum voluntary expirationExpiratory reserve volume: the maximum extra volume of air that can be expired by forceful expiration after the end of a normal tidal expirationResidual volume: the volume of air remaining in the lungs after the most foreceful expirationVital capacity: inspiratory resrve volume + tidal volume + expiratory reserve volume; the max amt of air a person can expel from the lugs after first filling the lungs to their maximum extent and then expiring to the maximum extentFunctional residual capacity: expiratory reserve volume + residual volume; the amt of air that remains in the lungs at the end of normal expirationTotal lung capacity: vital capacity + residual volume; maximum volume to which the lungs can be expanded with the greatest possible effortTidal volume: the volume of air inspired or expired with each normal breath
61T or FIn health, the greatest resistance to airflow occurs in small terminal bronchiolesFalseFalse: greatest resistance to airflow occurs in the lrg bronchi. This is b/c there are relatively few bronchi in comparison w/ abt 65K parallel terminal bronchioles, through each of which only a minute amt of air must pass. In dz conditions, the smaller broncioles often do play a greater role in determining airflow resistance for 2 reasons: 1) b/c their small size they are easily occluded 2) b/c they have a greater % of smooth muscle in the walls, they constrict easily
62The most important factor limiting flow rate during most of a forced expiration from total lung capacity is:Rate of contraction of expiratory musclesAction of diaphragmConstriction of bronchial smooth muscleElasticity of chest wallCompression of airways5
63What is the difference b/w anatomic and physiologic dead space? Anatomic dead space: represents the volume of conducting airwaysPhysiologic dead space: the part of the tidal volume which does not participate in gas exchange
64Which of the following are components of the conducting airways? Trachea, bronchioles, alveolar ducts, and bronchiBronchi, resp bronchioles and alveolar sacsBronchi, bronchioles, terminal bronchioles and respiratory bronchiolesTrachea, bronchi, bronchioles, and terminal bronchioles4: the components of the resp airways/zones are resp bronchioles, alveolar ducts and alveolar sacs
66Which of the following is NOT true about surfactant? Surfactant decreases alveolar surface tensionSurfactant is secreted primarily by type I pneumocytes as well as goblet cellsSurfactant is spread over the alveolar surface and reduces the surface tension to 1/12 to ½ of the surface tension of a pure water surfaceAs an alveolus becomes smaller, the surfactant molecules on the alveolar surface are squeezed together, increasing their concentrationAnswer: 2- surfactant is made of type II alveolar epithelial cells
67Which of the following statements is FALSE? Pulmonary surfactant: Reduces the surface tension of the alveolar lining liquidIs secreted by type II alveolar epithelial cellsContains dipalmitoyl phosphatidylcholineIncreases the work required to expand the lungHelps to prevent transudation of fluid from the capillaries into the alveolar spaces4
68References/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.
69Airway physiology and clinical function testing. Hoffman Airway physiology and clinical function testing. Hoffman. Vet Clinics 2007Small 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 ( ). 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.