Adobe Systems Respiratory system IV Lung diseases VLA 1. 12. 2020 Opakování •Pod pojmem dýchání rozumíme výměnu dýchacích plynů mezi vnitřním a zevním prostředím. •Někdy se používá pojem buněčné dýchání pro procesy spojené s tvorbou energie za spotřeby kyslíku v mitochondriích buněk. Anatomie dýchacího systému •Horní cesty dýchací •Dolní cesty dýchací •Plíce Hlavní funkce dýchacího systému •Ventilace •Difúze •Perfúze •Činnost respiračního systému úzce souvisí s činností oběhového systému, proto se někdy mohou poruchy oběhového systému manifestovat jako poruchy respirace. Funkce horních cest dýchacích •Zvlhčit a ohřát vzduch •Odstranit větší nečistoty •Relativní vlhkost vzduchu •Ztráty vody dýchacím systémem cca 0,5l/den Funkce dolních cest dýchacích •Křižovatka mezi dýchacími cestami a trávícím traktem. •Ochrana dýchacích cest před průnikem potravy – epiglotis, hlasivky – laryngeální spasmus Funkce plic •Vlastní výměník, ve kterém dochází k výměně plynů mezi alveolárním vzduchem a krví. Ventilace •Alveolární ventilace VA je rozdíl mezi celkovou plicní ventilací a ventilací mrtvého prostoru. VA=VT-VD •Ventilace je součin dechové frekvence a dechového objemu VA= f*(TV-DV) •Při růstu dechové frekvence a poklesu dechového objemu zůstává sice VT zachována ale VA klesá, protože relativně roste ventilace mrtvého prostoru. •Tlakový gradient •Nádech •Výdech •Aktivní a pasivní děje •Negativní tlak v pleurální dutině •Elasticita plic •Odpor dýchacích cest Perfúze •Výměna plynů mezi krví a alveolárním vzduchem probíhá jen tehdy pokud dochází ke kontaktu krve a vzduchu na dostatečně velké ploše alveolokapilární membrány po dostatečně dlouhou dobu. •Regulace vlivem hypoxie. •Respiračně perfúzní poměr •Filtrace krve – trombembolie, metastázy; rezervoár krve. Difúze •Na rychlosti difúze, respektive difúzním toku se podílí vlastnosti membrány, koncentrační gradient a velikost plochy. •Vůči různým plynům se difúzní membrána chová různě. •Oxid uhličitý difunduje snáze než kyslík 20x – při chorobných stavech bývá postižen přestup kyslíku více než přestup CO2. Hlavní typy poruch funkce dýchacího systému •Poruchy pleurální dutiny •Obstrukce dýchacích cest •Restrikční plicní choroby •Cirkulační plicní poruchy •Intersticiální plicní nemoci •Respirační selhání Odlišení dvou hlavních klinických kategorií •Obstrukční plicní choroby •Restrikční plicní choroby Pleurální dutina •Pleuritida •Exudát, transudát •Pneumothorax (zevní x vnitřní, otevřený, uzavřený, ventilový) •Atelektáza x kolaps plicní tkáně Obstrukce dýchacích cest •Obstrukce dolních dýchacích cest. Ovlivněn hlavně výdech, primárně snížení ventilace Asthma bronchiale •Extrinsic asthma •Intrinsic asthma •Otok, sekrece, spasmus •Chronický zánět •Chronic obstructive pulmonary disease –Chronická obstruktivní bronchitida –Emfyzém Emfyzém •Destrukce interalveolárních sept vedoucí ke hyperinflaci plicní tkáně a kolapsu malých dýchacích cest. •Kouření cigaret, defekt alfa1-antitripsinu (1% případů). Chronická bronchitida •Kouření a chronické infekce. •Hypersekrece hlenu a hypertrofie hlenovýchžláz s fibrózou stěny bronchu. Klinický obraz COPD - zjednodušeno •Pink puffer - emfyzematik s hyperventilací •Blue bloater - bronchitik s hypoxií Intersticiální plicní choroby •Pneumokoniózy •Sarkoidosa •Některé léky, ionizující záření •Autoimunitní choroby Poruchy krevního oběhu •Plicní embolie –Tromembolie –Jiné typy embolií •Plicní hypertenze –Prekapilární (pravolevý zkrat, embolie) –Kapilární (hypoxie) –Postkapilární (levostranné srdeční selhání) •Cor pulmonále ARDS •Acute respiratory distress syndrome •Popsán teprve v roce 1967 •Vyústění spousty etiopatogeneticky rozličných, velmi těžkých stavů •Poškození alveolokapilární membrány, deaktivace surfaktantu. Respirační selhání •Hypoxemie •Hypoxemie s hyperkapnií •Hypoventilace •Ventilačně perfúzní nepoměr •Poruchy difúze Adobe Systems Zápatí prezentace 8 Pathophysiology of pulmonary hypertension Adobe Systems Zápatí prezentace 9 Background normal anatomy and physiology Obsah obrázku zelenina Popis byl vytvořen automaticky Adobe Systems Zápatí prezentace 10 Anatomy review - schematic Adobe Systems Zápatí prezentace 11 Anatomy review - Realistic Adobe Systems Zápatí prezentace 12 Swan Ganz catheter placement Adobe Systems Zápatí prezentace 13 Why is pulmonary artery pressure normally low? Adobe Systems Zápatí prezentace 14 Abnormal anatomy and physiology Adobe Systems Zápatí prezentace 15 Abnormal PA pressures in real patients range from 30 to 100 mmHg Adobe Systems Zápatí prezentace 16 Ventricular septal defect and pulmonary embolism Adobe Systems Blood flow vs. Velocity of blood flow ÒOhm´s law: ÒBF=BP/R, BP=blood pressure, BF=blood flow, R= resistance of blood vessels ÒBF=BP/R Ò ÒVelocity of blood flow (v): ÒΠ x r2 . v = (constant !!!!!) ÒBlood vessels „like“ their natural (physiological) diameter and they have tendency to do it by remodelling of blood flow > Adobe Systems ̶Because flowing blood has mass and velocity it has kinetic energy (KE). This KE is proportionate to the mean velocity squared (V2; from KE = ½ mV2). Furthermore, as the blood flows inside a vessel, pressure is exerted laterally against the walls of the vessel; this pressure represents the potential or pressure energy (PE). The total energy (E) of the blood flowing within the vessel, therefore, is the sum of the kinetic and potential energies (assuming no gravitational effects) as shown below. ̶E = KE + PE (where KE ∝ V2) Therefore, E ∝ V2 + PE Blood flow energy Adobe Systems ̶Blood flow is driven by the difference in total energy between two points. Although pressure is normally considered as the driving force for blood flow, in reality it is the total energy that drives flow between two points (e.g., longitudinally along a blood vessel or across a heart valve). Throughout most of the cardiovascular system, KE is relatively low, so for practical purposes, it is stated that the pressure energy (PE) difference drives flow. When KE is high, however, adding KE to the PE significantly increases the total energy, E. To illustrate this, consider the flow across the aortic valve during cardiac ejection. Late during ejection, the intraventricular pressure (PE) falls slightly below the aortic pressure (PE), nevertheless, flow continues to be ejected into the aorta. The reason for this is that the KE of the blood as it moves across the valve at a very high velocity ensures that the total energy (E) in the blood crossing the valve is higher than the total energy of the blood more distal in the aorta. Blood as hemodynamic priority Adobe Systems ̶Kinetic energy and pressure energy can be interconverted so that total energy remains unchanged. This is the basis of Bernoulli's Principle. This principle can be illustrated by a blood vessel that is suddenly narrowed then returned to its normal diameter. In the narrowed region (stenosis), the velocity increases as the diameter decreases. Quantitatively, v ∝ 1/D2 because flow (BF) is the product of mean velocity (v) and vessel cross-sectional area (S) (BF = v ∙ D), and S is directly related to diameter (D) (or radius, r) squared (from S = π ∙ r2). If the diameter is reduced by one-half in the region of the stenosis, the velocity increases 4-fold. Because KE ∝ v2, the KE increases 16-fold. Assuming that the total energy is conserved within the stenosis (E actually decreases because of resistance), then the 16-fold increase in KE must result in a proportionate decrease in PE. Once past the narrowed segment, KE will revert back to its pre-stenosis value because the post-stenosis diameter is the same as the pre-stenosis diameter and flow is conserved. Because of the resistance of the stenosis, and the likelihood of turbulence, the post-stenosis PE and E will both fall. ̶To summarize this concept, blood flowing at higher velocities has a higher ratio of kinetic energy to potential (pressure) energy. Energy of blood flow and Bernoulli's Principle Adobe Systems Zápatí prezentace 21 Many causes of PAH*, Part 1 Adobe Systems Effect of pulmonary arterial hypertension (PAH) on SF-36-measured health-related quality of life (HRQoL) measures versus the normal population and other disease conditions [12–15]. Marion Delcroix, and Luke Howard Eur Respir Rev 2015;24:621-629 ©2015 by European Respiratory Society Effect of pulmonary arterial hypertension (PAH) on SF-36-measured health-related quality of life (HRQoL) measures versus the normal population and other disease conditions [12–15]. COPD: chronic obstructive pulmonary disease; SF-36: Medical Outcomes Study 36-item short form. Adobe Systems Zápatí prezentace 23 Precapillary vs. postcapillary PAH Continuing Cardiology Education, Volume: 4, Issue: 1, Pages: 2-12, First published: 27 July 2018, DOI: (10.1002/cce2.71) Pathophysiology of pulmonary hypertension Pathophysiological mechanisms of PAH. Environmental insults can contribute to PAEC damage and injury. In the healthy state, physiological repair processes restore normal lung function via proliferation of nearby ECs and/or the recruitment of circulating endothelial progenitor cells (EPCs). In PAH, pulmonary vascular cell damage contributes to the degeneration of microvasculature and/or arteriolar remodeling. In patients with hereditary PAH underlying genetic mutations are associated with increased susceptibility to PAEC damage and injury. [Adapted from: Foster et al.] with permission from the Canadian Cardiovascular Society. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. Adobe Systems is an important risk factor for disease progression and exacerbation risk. Relative pulmonary artery enlargement on computed tomography scan, defined by a pulmonary artery to aortic (PA:A) ratio >1, has been evaluated as a marker of pulmonary vascular disease. In healthy patients a PA:A ratio >0.9 is considered to be abnormal. The PA:A ratio has been compared with invasive hemodynamic parameters, primarily mean pulmonary artery pressure in various disease conditions and is more strongly correlated with mean pulmonary artery pressure in obstructive as compared with interstitial lung disease. In patients without known cardiac or pulmonary disease, the PA:A ratio is predictive of mortality, while in COPD, an elevated PA:A ratio is correlated with increased exacerbation risk, outperforming other well established predictors of these events. Pulmonary vascular disease Continuing Cardiology Education, Volume: 4, Issue: 1, Pages: 2-12, First published: 27 July 2018, DOI: (10.1002/cce2.71) Classification of pulmonary hypertension Pulmonary hypertension is classified into five distinct groups based on the findings and recommendations from world experts at the most recent World Symposium on Pulmonary Hypertension (Nice, France, 2013). IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. Adobe Systems Zápatí prezentace 27 IPAH Familial – BMPR2, ALK 1,Unknown Associated with PAH –Connective Tissue Disease (Scleroderma, SLE, MCTD, RA) –Congenital Heart Disease –Portal hypertension (5-7% of patients) –HIV (0.5% of patients) –Drugs/toxins (aminorex-, dexfenfluramine-, or fenfluramine- containing products, cocaine, methamphetamine) –Other: hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy Associated with venous/capillary involvement –Pulmonary veno-occlusive disease (evidence of pulmonary vascular congestion) –Pulmonary capillary hemangiomatosis Persistent PH of newborn. Group 1 PAH 1.1 Idiopathic PAH 1.2 Heritable PAH 1.2.1 BMPR2 1.2.2 ALK-1, ENG, SMAD9, CAV1, KCNK3 1.2.3 Unknown 1.3 Drug and toxin induced 1.4 Associated with: 1.4.1 Connective tissue disease 1.4.2 HIV infection 1.4.3 Portal hypertension 1.4.4 Congenital heart diseases 1.4.5 Schistosomiasis 1 0 Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis 1 00 Persistent pulmonary hypertension of the newborn (PPHN) Adobe Systems Zápatí prezentace 28 •Group 2: Pulmonary hypertension due to left heart disease –2.1 Left ventricular systoli c dysfunction –2.2 Left ventricular diasto lic dysfunction –2.3 Valvular disease –2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies – •Group 3: Pulmonary hypertension associated with lung disease and/or hypoxemia –3.1 Chronic obstructive pulmonary disease –3.2 Interstitial lung disease –3.3 Other pulmonary diseases with mixed restrictive and obstruc- –tive pattern –3.4 Sleep-disordered breathing –3.5 Alveolar hypoventilation disorders –3.6 Chronic exposure to high altitude –3.7 Developmental lung diseases Group 2-3 Continuing Cardiology Education, Volume: 4, Issue: 1, Pages: 2-12, First published: 27 July 2018, DOI: (10.1002/cce2.71) Differences JCM | Free Full-Text | Pulmonary Arterial Hypertension and ... Schematic representations of pulmonary hypertension. Representation of site of initiation of elevated pulmonary arterial pressure of precapillary pulmonary hypertension, postcapillary pulmonary hypertension, and CTEPH. L.V., left ventricle; PH, pulmonary hypertension; R.A., right atrium; R.V., right ventricle. [Adapted from: Gordeuk et al.] IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. Adobe Systems Zápatí prezentace 30 Group 4-5 •Group 4: Pulmonary hypertension due to chronic thrombotic and/or embolic disease –Thromboembolic obstruction of proximal pulmonary arteries –Thromboembolic obstruction of distal pulmonary arteries •Group 5: Miscellaneous 5.1 Hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy 5.2 Systemic disorders: sarcoidosis, pulmonary histiocytosis,lymphangioleiomyomatosis 5.3 Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders 5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental PH Adobe Systems Zápatí prezentace 31 Adobe Systems Zápatí prezentace 32 Group 1 - Pathophysiology •Exact mechanism – unknown. •Multifactorial. 1)Excessive vasoconstriction -abnormal function or expression of potassium channels in the smooth muscle cells . 2)Endothelial dysfunction leads to chronically impaired production of vasodilator and Vasoconstrictors (NO, prostacyclin, thromboxane A2 and endothelin-1) Adobe Systems Zápatí prezentace 33 3)Reduced plasma levels of other vasodilator and antiproliferative substances such as vasoactive intestinal peptide 4)In the adventitia there is increased production of extracellular matrix including collagen, elastin, fibronectin. Inflammatory cells and platelets (through the serotonin pathway) 5)Prothrombotic abnormalities have been demonstrated in PAH patients, and thrombi are present in both the small distal pulmonary arteries and the proximal elastic pulmonary arteries Adobe Systems Zápatí prezentace 34 1.Tunica media hypertrophy 2.Tunica intima proliferation 3.Fibrotic changes of tunica intima 4. concentric eccentric 4.Tunica adventitial thickening with moderate perivascular infiltrates 5.Complex lesions Plexiform Dilated 6.Thrombotic lesions. Adobe Systems Zápatí prezentace 35 Group 2 - Pathophysiology •Due to lt. heart diseases: •Pulmonary venous hypertension-most common cause •Usually due to left-sided heart disease (valvular, coronary or myocardial), obstruction to blood flow downstream from the pulmonary veins. •Reversibility is variable, dependent on lesion. Adobe Systems Zápatí prezentace 36 Group 3 - Pathophysiology PH due to lung diseases and/or hypoxia: Multiple 1)hypoxic vasoconstriction, 2)mechanical stress of hyperinflated lungs, 3)loss of capillaries – emphysema, fibrosis 4)inflammation, and toxic effects of cigarette smoke. 5)endothelium-derived vasoconstrictor–vasodilator imbalance. Hypoxia induced pulmonary vasoconstriction and anatomical destruction of the vascular bed due to high pulmonary resistance and ultimately RV failure. Adobe Systems Zápatí prezentace 37 Group 4-5 - Pathophysiology •CTEPH: non-resolution of acute embolic masses which later undergo fibrosis leading to mechanical obstruction of pulmonary arteries is the most important process. •PH with unclear and/or multifactorial mechanisms. Adobe Systems Zápatí prezentace 38 ▪Unexplained dyspnea despite multiple diagnostic tests ▪Typical symptoms (look for Raynaud’s) ▪Comorbid conditons: ▪CREST, liver disease, HIV, sickle cell, OSA ▪Family history of PAH ▪History of stimulant/anorexigen use Reasons to suspect PH Adobe Systems Zápatí prezentace 39 Symptoms of PH Dyspnea Fatigue Near syncope/syncope Chest pain Palpitations LE edema Hoarseness of voice (Ortners syndrome) 60% 19% 13% 7% 5% 3% 2% Adobe Systems Zápatí prezentace 40 Pathophysiology of ARDS ARDS stats •170,000 cases/year •10 percent of ICU patients diagnosed with ARDS •78 percent within 48 hours of admission •23 percent of ventilated patients develop ARDS -Most develop ARDS within 24 hours of ventilation •Ventilator stats - 8 day LOS -35 percent received >8 ml/kg PBW tidal volumes -82 percent received <12 PEEP •Cost: $115,000 per hospital stay • 2016 ARDS epidemiology Severe ARDS survivors •Ventilator LOS 11 days •ICU LOS 14 days •Hospital LOS 26 days • • Bellaini, et al (2017). Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8),: 788-800. The above describes a 2017 analysis of ARDS worldwide, 459 ICUs, 50 countries over 4 weeks in Winter 2014- 3022 patients studied Bellaini, et al (2017) Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8), 788-800. Acute hypoxemic respiratory failure defined: p/f <300, new pulmonary parenchymal xray/CT abnormalities, and ventilator support with continuous CPAP Identification and diagnosis of ARDS is lacking •40 percent of all cases never diagnosed with ARDS •Only 34 percent of ARDS cases being identified when criteria is met Opportunity to improve outcomes with early identification and intervention 2016 ARDS epidemiology continued IDENTIFICATION AND DIAGNOSIS OF ARDS IS LACKING •40% of all cases never diagnosed with ARDS •Only 34% of ARDS cases being identified when criteria is met Opportunity to improve outcomes with early identification and intervention Bellaini, et al (2017). Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8),: 788-800. This table demonstrates the reduction in survivability every additional day a patient has ARDS. 100% survivability at day one, significantly dropping with severe ARDS. Visual representation of early intervention = improved mortality Bellaini, et al (2017) Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8), 788-800. Direct injury •Pulmonary contusion •Pneumonia •Aspiration of gastric contents •Inhalation of toxins •Pulmonary infection (flu/H1N1) •Oxygen toxicity Indirect injury •Sepsis syndrome •Multiple transfusions •Trauma •Pancreatitis •Cardiopulmonary bypass •DIC Causes of ARDS •Bellaini, et al (2017). Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8),: 788-800. •2000 ARDSnet study- patient population diagnoses.The New England Journal of Medicine, (342) 18. Pie chart is statistics from the Bellani epidemiology report Bellaini, et al (2016) Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8), 788-800. http://www.aafp.org/afp/2002/0501/p1823.html http://www.aafp.org/afp/2003/0115/p315.html Common causes: 2000 ARDSnet study- patient population diagnoses http://www.nejm.org/doi/pdf/10.1056/NEJM200005043421801 Phases of ARDS •Phase no. 1 – Injury or Exudative 1-7 days post-injury, 50 percent of cases within 24 hours of event •Pathophysiology •Reduced blood flow to lungs •Inflammatory mediator release •Increased capillary permeability •Intrapulmonary shunting begins •Symptoms •Refractory hypoxemia •Increased respiratory rate •Decreased tidal volume •Respiratory alkalosis •CXR infiltrates •Levy, B., Shapiro, S., and Choi., A. Acute Respiratory Distress Syndrome. Critical Care Medicine Chapter 268, retrieved from http://media.axon.es/pdf/83592.pdf •Zompatori, M., Ciccarese, F., and Fasano, L. Overview of current lung imaging in acute respiratory distress syndrome. European Respiratory Review, 2014; 23: 519-530. *****About 50% of patients who develop ARDS do so within 24 hours of the inciting event. 72 hours post event 85% of patients exhibit symptoms*** http://www.aafp.org/afp/2003/0115/p315.html All patients progress differently through these phases. Please note that some patients may be in stage two much earlier than 7 days. Phase no. 2 – Reparative or Proliferative 1-2 weeks after initial injury Pathophysiology •Increased capillary permeability •Protein and fluid leakage •Pulmonary edema •Alveolar collapse Symptoms •Decreased lung compliance •Worsened hypoxia •CXR “white out” Phases of ARDS Levy, B., Shapiro, S., and Choi., A. Acute Respiratory Distress Syndrome. Critical Care Medicine Chapter 268, retrieved from http://media.axon.es/pdf/83592.pdf Zompatori, M., Ciccarese, F., and Fasano, L. Overview of current lung imaging in acute respiratory distress syndrome. European Respiratory Review 2014; 23: 519-530. Ventilator-induced lung injury is initiated by the application of excessive stress and strain to the lung. High levels of mechanical stress and strain that occur when high airway pressures and volumes are delivered can disrupt the pulmonary fibroelastic skeleton (baro or volutrauma). This trauma triggers a secondary response referred to as biotrauma. Moderate degrees of stress and strain related to the cyclic opening and closing of the parts of the lungs causes atelectrauma, which may directly induce the release of inflammatory mediators and noxious proteinases. If reparative phase persists, fibrous tissue results; if this phase is arrested, lesions are able to resolve. Marini JJ, Gattinoni L. Ventilatory management of acute respiratory distress syndrome: a consensus of two. Crit Care Med 2004;32:250-5 Phase no. 3 – Fibrotic or Chronic 2-3 weeks after injury Pathophysiology •Fibrous tissue throughout lung •Diffuse scarring Symptoms •Severe acidosis on ABG •Overwhelming hypoxemia •Multi-organ dysfunction (MODS) •Hypotension •Low urine output Phases of ARDS Normal Human Lung Capillaries Lung Capillaries – 14 day ARDS Zompatori, M., Ciccarese, F., and Fasano, L. Overview of current lung imaging in acute respiratory distress syndrome. European Respiratory Review, 2014; 23: 519-530. Early ARDS Fibrotic ARDS It is important to consider how much oxygen a patient requires to achieve their PaO2 on an ABG. The P/F ratio is a very useful tool to monitor your patient’s oxygenation status. PaO2 / FiO2= P/F Ratio Healthy adult PaO2 = 80-100 mmHg Room air = 21 percent oxygen 100/.21 = P/F ratio 476 for a healthy adult Calculating PaO2 / FiO2 ratio European Society of Intensive Care. Medicine, Journal of American Medical Association June 2012: 307 (23). PaO2 FiO2 = P/F ratio Calculating PF ratio is a great tool for your everyday nursing assessments. While we were taught that a ‘normal’ PaO2 is 80-100, we must think beyond that and consider how much oxygen a patient is taking in to get to that “normal” PaO2. So think about it like this- if your patient is on 40% FiO2 and has a PaO2 of 80, they are requiring TWICE as much oxygen as a healthy person does to get to the same ‘normal’ number. To calculate a P/F ratio, divide the PaO[2] by the FiO[2]. For example: •If normal PaO[2] is 80 – 100 and the FiO[2] at room air is 21%, •100/0.21 = 476 •The P/F ratio is 476. Let’s use 476 as a benchmark for normal. A P/F ratio of around 476 would be an indicator of an efficient exchange of gases. Let’s do another: •If the PaO2 is 80 and the FiO2 delivered is 40%, •80/0.40 •The P/F ratio is 200 A P/F ratio of 200 is indicative of a possible intrapulmonary shunt and possible ARDS if the patient meets other diagnostic criteria. Consider the amount of oxygen the patient is taking in at 40%. Would you be concerned about this patient? When you consider the fact that the patient is taking in 2 times the amount of oxygen in room air to get to the same number of 80… Calculating P/F can really make a difference in how you view your patients! 2012 Berlin ARDS definition 2012 BERLIN ARDS DEFINITION Mild Moderate Severe Timing Acute onset within 1 week of known clinical consult or new/worsening symptoms Hypoxemia PaO2 / FiO2 <300->200 with PEEP ≥ 5 PaO2 / FiO2 <200->100 with PEEP ≥ 5 PaO2 / FiO2 ≤100 with PEEP ≥ 5 Origin of Edema Respiratory failure not fully explained by cardiac failure or fluid overload objective assessment if no risk factors present Radiologic Abnormalities Bilateral chest opacities Bilateral chest opacities Opacities involving at least 3 quadrants 1.Munro, C.L. and Savel, R. H. A, Journal of Critical Care, Sept. 2012. http://ajccjournals.org/content/21/5/305. 2.European Society of Intensive Care. Medicine, Journal of American Medical Association, June 2012: 307 (23). New definition removed the confusion of ALI vs ARDS and simply calls each type mild, moderate, severe The limits found included no measurement of PEEP, the lack of standard use of wedge pressure measurement, and the limited description of lung quadrants affected. •The classifications of ALI/ARDS created confusion A publication was released in the Intensive Care Medicine journal titled, “An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital.” This research with many of the same researchers who were part of the consensus panel and the Professor Guerin research were co-authors. They assessed 278 patients, of which 18 (6.5%) did not comply with the Berlin criterion of PEEP and Pa02/FiO2 ratios. This study at a single site did not validate the Berlin definition of ARDS. Neither the Pa02/Fi02 or the stratification by severity at study entry was independently associated with mortality. A weakness of the study was “covariates were measured at the time of inclusion and management afterwards was not recorded. Therefore, the multivariate analysis of mortality did not include variables that may impact on patient outcomes, like prone positioning or fluid balance control. Reference: Intensive Care Med (2013) 39:2161 – 2170 DOA 10.1007/s00134-013-3122-6 ARDS mortality rates 2012 to 2016 Bellaini, et al (2017). Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8): 788-800. REFERENCE: 1Amaral, Rubenfeld. The Future of Critical Care. Current Opinion in Critical Care. 2009;15:308-313 2Phua, Badia, et al. Has Mortality from Acute Respiratory Distress Syndrome Decreased Over Time. Am Respir Crit Care Med. 2009; 179: 220-227 3Johnson, E.R. & Matthay, M.A., Acute Lung Injury: Epidemiology, Pathogenesis, and Treatment. J Aerosol Med Pulm Drug Deliv. 2010 23(4): 243-252. 4Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. 5 www.ncbi.nim.hin.gov/pmc/articles/PMC3133560 http://www.uptodate.com/contents/acute-respiratory-distress-syndrome-prognosis-and-outcomes-in-adul ts#H3 •Severity of hypoxemia •Infection/sepsis •Multi-organ dysfunction •Positive fluid balance •Age •Patients with higher plateau pressures have higher risks of death (>20 cm H20) ARDS predictors of mortality Bellaini, et al (2017). Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8): 788-800. The graph represents the relationship between probability of death and plateau pressure. High plateau pressures lead to increased risk for death based on the recent Bellaini ARDS epidemiology study. REFERENCE: 1Amaral, Rubenfeld. The Future of Critical Care. Current Opinion in Critical Care. 2009;15:308-313 2Phua, Badia, et al. Has Mortality from Acute Respiratory Distress Syndrome Decreased Over Time. Am Respir Crit Care Med. 2009; 179: 220-227 3Johnson, E.R. & Matthay, M.A., Acute Lung Injury: Epidemiology, Pathogenesis, and Treatment. J Aerosol Med Pulm Drug Deliv. 2010 23(4): 243-252. 4Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. 5 www.ncbi.nim.hin.gov/pmc/articles/PMC3133560 6Bellaini, et al (2017) Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units of 50 countries. Journal of American Medical Association, 315 (8), 788-800. Let’s do a quick analysis of an ICU patient diagnosed with pneumonia and recently intubated: ABG pH 7.12 PaO2 80 HCO3 19 CO2 60 FiO2 80% What is their P/F ratio and their stage in ARDS? P/F ratio calculation P/F ratio 133 Moderate ARDS PaO2 FiO2 80 .6 What is a normal paO2 for ARDS? What are the considerations Evidence-based / standard of care Treatment modalities for ARDS Salvage therapy in ARDS Physician/facility specific Ask the nurses: do they remember tidal volumes of 800-1000? Most reply yes, but they do not see that anymore, now they see tidal volumes around 400-500. Would be a great time to point out recent evidence showing that even after a large study (ARDSnet) showing low tidal volume as standard of care, that still 35% of patients aren’t receiving the low tidal volume ventilation. May explain why it’s so difficult to change practice even after the great evidence we have seen with pp. Interesting to note: while low tidal volume is standard of care and has been for years, a recent study (2016 Bellaini) found that 35% of patients with ARDS were ventilated with >8ml/kg tidal volumes, and 83% received PEEP <12! Why does prone positioning work? Ventilation benefits Cardiovascular benefits Figure 1. Pelosi, et al. Prone position in acute respiratory distress syndrome. European Respiratory Journal, 2002; 20(4): 1017-1028 Oxygenation benefits There are several reasons why prone positioning is a desirable treatment for ARDS. In the next several slides, each of these reasons will be discussed in depth. C:\Users\usaddhij02\Pictures\exhausted-runner.jpg What do you do when you are out of breath? Ask the clinicians, what do they do when they’re out of breath? Do they lay flat on their back and breathe out of a straw? There are many reasons why we use the tripod position to catch our breath- let’s review. •Shape of the lungs Dependent fluid accumulation •Alveolar recruitment Mobilization of secretions •Downward shape of esophagus Secretions! • Oxygenation benefits Mackenzie, CF. Anatomy, Physiology, and pathology of the prone position and postural drainage. Critical Care Medicine, 2001;29(5): 1084-1085. ~ 75 percent of patients will have an increase in oxygenation in the prone position. Guerin, 2014 The picture of the lung depicts its’ shape supine, imagine the secretions accumulating in that large surface area. Imagine the secretions in the alveoli mobilizing with the position change. The last blue picture depicts the pressure on the alveoli in the supine position, causing compression of the dependent regions of the lung supine. •Relief of pressure of heart on lungs -Improved tidal volume -Reduced pressure on right ventricle §Supine compression of the lungs from the heart is ~20 percent §Prone compression of the lungs is ~3.5 percent •Perfusion preferentially directed to dorsal lung regions •Removal of abdominal pressure reduces pressure on vena cava to improve venous return Cardiovascular benefits •Murray, T. A. and Patterson, L.A. Prone positioning of trauma patients with acute respiratory distress syndrome and open abdominal incisions. Critical Care Nurse, June 2002; 22 (3): 52-56. •From Cardiopulmonary Anatomy & Physiology 4th edition by DESJARDINS. ©2002. Reprinted with permission of Delmar Learning, a division of Thomson Learning: www.thomsonrights.com. Fax 800 730-2215 •Anzueto, A., and Gattinoni, L. Prone position and acute respiratory distress syndrome. Acute Respiratory Distress Syndrome. 2003. New York: Marcel Dekker, Inc. Physiologic effects prone vs. supine Supine Prone Decreased lung volumes Increased lung volumes Accumulation of atelectasis in dependent regions Facilitation of secretion drainage Refractory hypoxemia exacerbated by accumulation of secretions in dependent regions of lungs Increased oxygenation due to mobilization of secretions and alveolar recruitment Regional and gravitational differences in lungs increase V/Q mismatch and increased stress and strain on the lung Optimized ventilation due to smaller vertical pleural pressure gradient, increased FRC and more even gas volume distribution Let’s review– is there really any benefit to the supine position in ARDS? FRC- functional residual capacity- volume of air present in lungs @ end of expiration Prone- increased FRC related to the relief of pressure on the lungs from the abdomen, relief of pressure on the lung by the heart All of these effects demonstrate why the prone position is much more beneficial to patients in the supine position. It also demonstrates why patients usually do not tolerate the supine position when they are later in the disease process of ARDS. At enrollment ARDS lung and effect of proning After 2 days of proning Images courtesy of Frank Sebat, M.D. Both of these CT scans from Dr. Sebat’s study are the same patient in the supine position -- one at initial enrollment and the second CT scan demonstrating improvement in patient after just 2 days of prone positioning. Note the size of an ARDS patient’s heart compared to the previous picture of a healthy CT scan. Also note where the secretions develop. 1.Alteration in lung parenchyma. 2. 2.Diseases of the pleura, chest wall or neuromuscular apparatus. Physiologically restrictive lung diseases are defined by reduced total lung capacity, vital capacity and functional residual capacity, but with preserved air flow. Restrictive lung diseases Restrictive lung diseases may be divided into the following groups: ■Intrinsic lung diseases (diseases of the lung parenchyma) ■Extrinsic disorders (extra-parenchymal diseases) These diseases cause either: ■Inflammation and/or scarring of lung tissue (interstitial lung disease) or ■Fill the air spaces with exudate and debris (pneumonitis). ■These diseases are classified further according to the etiological factor. Intrinsic lung diseases The chest wall, pleura and respiratory muscles are the components of respiratory pump. Disorders of these structures will cause lung restriction and impair ventilatory function. These are grouped as: ■Non-muscular diseases of the chest wall. ■Neuromuscular disorders. Extrinsic lung disorders Intrinsic lung diseases: ■Diffuse parenchymal disorders cause reduction in all lung volumes. ■This is produced by excessive elastic recoil of the lungs. ■Expiratory flows are reduced in proportion to lung volumes. ■Arterial hypoxemia is caused by ventilation/perfusion mismatch. ■Impaired diffusion of oxygen will cause exercise- induced desaturation. ■Hyperventilation at rest secondary to reflex stimulation. Pathophysiology Extrinsic Disorders ■Diseases of the pleura, thoracic cage, decrease compliance of respiratory system. ■There is reduction in lung volumes. ■Secondarily, atelectasis occurs leading to V/Q mismatch ➜ hypoxemia. ■The thoracic cage and neuromuscular structures are a part of respiratory system. ■Any disease of these structures will cause restrictive disease and ventilatory dysfunction. Diseases of the Lung Parenchyma EM in Pulmonary Fibrosis Structure of the Alveolar Wall Diffuse Interstitial Pulmonary Fibrosis ■Synonyms: idiopathic pulmonary fibrosis, interstitial pneumonia, cryptogenic fibrosing alveolitis. Pathology ■Thickening of interstitium. ■Initially, infiltration with lymphocytes and plasma cells. ■Later fibroblasts lay down thick collagen bundles. ■These changes occur irregularly within the lung. ■Eventually alveolar architecture is destroyed – honeycomb lung Pathogenesis Unknown, may be immunological reaction. Clinical Features ■Uncommon disease, affects adults in late middle age. ■Progressive exertional dyspnea, later at rest. ■Non-productive cough. ■Physical examination shows finger clubbing, fine inspiratory crackles throughout both lungs. ■Patient may develop respiratory failure terminally. ■The disease progresses insidiously, median survival 4-6 years. Pulmonary Function ■Spirometry reveals a restrictive pattern. FVC is reduced, but FEV1/FVC supernormal. ■All lung volumes – TLC, FRC, RV – are reduced. ■Pressure volume curve of the lung is displaced downward and flattened. Gas Exchange ■Arterial PaO2 and PaCO2 are reduced, pH normal. ■On exercise PaO2 decreases dramatically. ■Physiologic dead space and physiologic shunt and VQ mismatch are increased. ■Diffuse impairment contributes to hypoxemia on exercise. ■There is marked reduction in diffusing capacity due to thickening of blood gas barrier and VQ mismatch. Diagnosis ■Diagnosis is often suggested by history, chest radiograph and high resolution CT scan of the lungs. ■If old chest x-rays show classical disease, absence of other disease processes on history and no occupational or environmental exposure – clinical diagnosis can be made. ■In other cases a surgical lung biopsy is obtained. Thank you for attention 76