Respiratory Physiology
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Pulmonary Surfactant: the Key to the Evolution of Air Breathing Christopher B
Pulmonary Surfactant: The Key to the Evolution of Air Breathing Christopher B. Daniels and Sandra Orgeig Department of Environmental Biology, University of Adelaide, Adelaide, South Australia 5005, Australia Pulmonary surfactant controls the surface tension at the air-liquid interface within the lung. This sys- tem had a single evolutionary origin that predates the evolution of the vertebrates and lungs. The lipid composition of surfactant has been subjected to evolutionary selection pressures, partic- ularly temperature, throughout the evolution of the vertebrates. ungs have evolved independently on several occasions pendent units, do not necessarily stretch upon inflation but Lover the past 300 million years in association with the radi- unpleat or unfold in a complex manner. Moreover, the many ation and diversification of the vertebrates, such that all major fluid-filled corners and crevices in the alveoli open and close vertebrate groups have members with lungs. However, lungs as the lung inflates and deflates. differ considerably in structure, embryological origin, and Surfactant in nonmammals exhibits an antiadhesive func- function between vertebrate groups. The bronchoalveolar lung tion, lining the interface between apposed epithelial surfaces of mammals is a branching “tree” of tubes leading to millions within regions of a collapsed lung. As the two apposing sur- of tiny respiratory exchange units, termed alveoli. In humans faces peel apart, the lipids rise to the surface of the hypophase there are ~25 branches and 300 million alveoli. This structure fluid at the expanding gas-liquid interface and lower the sur- allows for the generation of an enormous respiratory surface face tension of this fluid, thereby decreasing the work required area (up to 70 m2 in adult humans). -
The Oxyhaemoglobin Dissociation Curve in Critical Illness
Basic sciences review The Oxyhaemoglobin Dissociation Curve in Critical Illness T. J. MORGAN Intensive Care Facility, Division of Anaesthesiology and Intensive Care, Royal Brisbane Hospital, Brisbane, QUEENSLAND ABSTRACT Objective: To review the status of haemoglobin-oxygen affinity in critical illness and investigate the potential to improve gas exchange, tissue oxygenation and outcome by manipulations of the oxyhaemoglobin dissociation curve. Data sources: Articles and published peer-review abstracts. Summary of review: The P50 of a species is determined by natural selection according to animal size, tissue metabolic requirements and ambient oxygen tension. In right to left shunting mathematical modeling indicates that an increased P50 defends capillary oxygenation, the one exception being sustained hypercapnia. Increasing the P50 should also be protective in tissue ischaemia, and this is supported by modeling and experimental evidence. Most studies of critically ill patients have indicated reduced 2,3-DPG concentrations. This is probably due to acidaemia, and the in vivo P50 is likely to be normal despite low 2,3-DPG levels. It may soon be possible to achieve significant P50 elevations without potentially harmful manipulations of acid-base balance or hazardous drug therapy. Conclusions: Despite encouraging theoretical and experimental data, it is not known whether manipulations of the P50 in critical illness can improve gas exchange and tissue oxygenation or improve outcome. The status of the P50 may warrant more routine quantification and consideration along with the traditional determinants of tissue oxygen availability. (Critical Care and Resuscitation 1999; 1: 93-100) Key words: Critical illness, haemoglobin-oxygen affinity, ischaemia, P50, tissue oxygenation, shunt In intensive care practice, manipulations to improve in the tissues. -
New Spirometry Interpretation Algorithm Primary Care Respiratory Alliance of Canada Approach
Critical Appraisal New spirometry interpretation algorithm Primary Care Respiratory Alliance of Canada approach Anthony D. D’Urzo MD MSc CCFP FCFP Itamar Tamari MD CCFP FCFP Jacques Bouchard MD Reuven Jhirad MD CCFP FCFP Pieter Jugovic MD MSc CCFP Clinical question Is there a need for a new spirometry interpretation algorithm that contains decision-making criteria consistent with current guidelines on asthma1 and chronic obstructive pulmonary disease (COPD)2 diagnosis? Using spirometry to distinguish between COPD and asthma Office spirometry provides valuable information about the relationship between flow and volume in relation to lung function and can be useful for diagnosing common conditions such as asthma and COPD.1,2 Mechanical abnor- malities of the respiratory system can be classified as either obstructive (flow-related) or restrictive (volume-related) ventilatory defects; obstructive defects are much more common in clinical practice. The relationship between flow and volume is described well by BOTTOM LINE • An algorithm commonly promoted in the ratio of the forced expiratory volume in 1 second (FEV1) to the forced vital capacity (FVC). These measurements can be easily obtained with a primary care is limited by its focus on using simple office spirometer during a forced expiratory maneuver. The ratio changes in forced expiratory volume in 1 second (FEV ) to distinguish asthma from of FEV1 to FVC can be useful to identify obstructive, restrictive, and com- 1 bined (obstructive-restrictive) defects, but it is important to recognize that chronic obstructive pulmonary disease total lung capacity, a more sophisticated measurement (and not the FVC), (COPD). The new algorithm consolidates is the best measurement to confirm a diagnosis of pulmonary restriction.3 current spirometric concepts that are consistent with both asthma and COPD Traditionally an FEV1-FVC ratio below 0.70 has been used to define a pure obstructive defect if the FVC is within normal limits. -
Oxygenation and Oxygen Therapy
Rules on Oxygen Therapy: Physiology: 1. PO2, SaO2, CaO2 are all related but different. 2. PaO2 is a sensitive and non-specific indicator of the lungs’ ability to exchange gases with the atmosphere. 3. FIO2 is the same at all altitudes 4. Normal PaO2 decreases with age 5. The body does not store oxygen Therapy & Diagnosis: 1. Supplemental O2 is an FIO2 > 21% and is a drug. 2. A reduced PaO2 is a non-specific finding. 3. A normal PaO2 and alveolar-arterial PO2 difference (A-a gradient) do NOT rule out pulmonary embolism. 4. High FIO2 doesn’t affect COPD hypoxic drive 5. A given liter flow rate of nasal O2 does not equal any specific FIO2. 6. Face masks cannot deliver 100% oxygen unless there is a tight seal. 7. No need to humidify if flow of 4 LPM or less Indications for Oxygen Therapy: 1. Hypoxemia 2. Increased work of breathing 3. Increased myocardial work 4. Pulmonary hypertension Delivery Devices: 1. Nasal Cannula a. 1 – 6 LPM b. FIO2 0.24 – 0.44 (approx 4% per liter flow) c. FIO2 decreases as Ve increases 2. Simple Mask a. 5 – 8 LPM b. FIO2 0.35 – 0.55 (approx 4% per liter flow) c. Minimum flow 5 LPM to flush CO2 from mask 3. Venturi Mask a. Variable LPM b. FIO2 0.24 – 0.50 c. Flow and corresponding FIO2 varies by manufacturer 4. Partial Rebreather a. 6 – 10 LPM b. FIO2 0.50 – 0.70 c. Flow must be sufficient to keep reservoir bag from deflating upon inspiration 5. -
Asthma Initiative Content
WAO Symposium Why Are Small Airways Important In Asthma? “Physiology Of Small Airways Disease” Thomas B Casale, MD Professor Of Medicine Chief, Allergy/Immunology Creighton University Omaha, NE USA Disease Process in Asthma is Located in All Parts of Bronchial Tree Including Small Airways and Alveoli Workgroep Inhalatie Technologie, Jun 1999. Relevant Questions On Small Airway Involvement In Asthma • How can „small airway disease‟ be defined? • What is the link between small airway abnormalities and clinical presentation in asthma ? • When does small airway involvement become relevant in the natural history of the disease? • Is it possible to reverse small airway abnormalities with pharmacological treatment? Contoli et al Allergy 2010; 65: 141–151 Pathophysiologic Changes in the Small Airways of Asthma Patients Transbronchial Biopsies 1 Lumen occlusion 2 Subepithelial fibrosis 3 Increase in smooth muscle mass 4 Inflammatory infiltrate 1 Immunostaining of eosinophils in small airway with major basic protein (in red) 2 Shows large number of eosinophils around the small airway Contoli M, et al. Allergy. 2010;65:141-151. Structural Alterations in Small Airways Associated With Fatal Asthma Small airway of a Small airway of a control subject subject with fatal asthma Mucus plugging Structural alterations in small airways have been implicated as an underlying reason for increased asthma severity and AHR….. Difficult to control asthma. Mauad T, et al. Am J Respir Crit Care Med. 2004;70:857-862. Differences In ECM Composition In Small Airways Between Fatal Asthma And Controls Dolhnikoff et al, JACI 2009; 123:1090-1097 Is There Differential Inflammation in Proximal and More Distal Airways? • Some studies suggest that the cellular infiltrate increases toward the periphery, but others show similar or decreased infiltration – May reflect heterogeneity of asthma as well as the different methods used in the studies . -
Respiratory Support
Intensive Care Nursery House Staff Manual Respiratory Support ABBREVIATIONS FIO2 Fractional concentration of O2 in inspired gas PaO2 Partial pressure of arterial oxygen PAO2 Partial pressure of alveolar oxygen PaCO2 Partial pressure of arterial carbon dioxide PACO2 Partial pressure of alveolar carbon dioxide tcPCO2 Transcutaneous PCO2 PBAR Barometric pressure PH2O Partial pressure of water RQ Respiratory quotient (CO2 production/oxygen consumption) SaO2 Arterial blood hemoglobin oxygen saturation SpO2 Arterial oxygen saturation measured by pulse oximetry PIP Peak inspiratory pressure PEEP Positive end-expiratory pressure CPAP Continuous positive airway pressure PAW Mean airway pressure FRC Functional residual capacity Ti Inspiratory time Te Expiratory time IMV Intermittent mandatory ventilation SIMV Synchronized intermittent mandatory ventilation HFV High frequency ventilation OXYGEN (Oxygen is a drug!): A. Most infants require only enough O2 to maintain SpO2 between 87% to 92%, usually achieved with PaO2 of 40 to 60 mmHg, if pH is normal. Patients with pulmonary hypertension may require a much higher PaO2. B. With tracheal suctioning, it may be necessary to raise the inspired O2 temporarily. This should not be ordered routinely but only when the infant needs it. These orders are good for only 24h. OXYGEN DELIVERY and MEASUREMENT: A. Oxygen blenders allow O2 concentration to be adjusted between 21% and 100%. B. Head Hoods permit non-intubated infants to breathe high concentrations of humidified oxygen. Without a silencer they can be very noisy. C. Nasal Cannulae allow non-intubated infants to breathe high O2 concentrations and to be less encumbered than with a head hood. O2 flows of 0.25-0.5 L/min are usually sufficient to meet oxygen needs. -
Respiratory Therapy Pocket Reference
Pulmonary Physiology Volume Control Pressure Control Pressure Support Respiratory Therapy “AC” Assist Control; AC-VC, ~CMV (controlled mandatory Measure of static lung compliance. If in AC-VC, perform a.k.a. a.k.a. AC-PC; Assist Control Pressure Control; ~CMV-PC a.k.a PS (~BiPAP). Spontaneous: Pressure-present inspiratory pause (when there is no flow, there is no effect ventilation = all modes with RR and fixed Ti) PPlateau of Resistance; Pplat@Palv); or set Pause Time ~0.5s; RR, Pinsp, PEEP, FiO2, Flow Trigger, rise time, I:E (set Pocket Reference RR, Vt, PEEP, FiO2, Flow Trigger, Flow pattern, I:E (either Settings Pinsp, PEEP, FiO2, Flow Trigger, Rise time Target: < 30, Optimal: ~ 25 Settings directly or by inspiratory time Ti) Settings directly or via peak flow, Ti settings) Decreasing Ramp (potentially more physiologic) PIP: Total inspiratory work by vent; Reflects resistance & - Decreasing Ramp (potentially more physiologic) Card design by Respiratory care providers from: Square wave/constant vs Decreasing Ramp (potentially Flow Determined by: 1) PS level, 2) R, Rise Time ( rise time ® PPeak inspiratory compliance; Normal ~20 cmH20 (@8cc/kg and adult ETT); - Peak Flow determined by 1) Pinsp level, 2) R, 3)Ti (shorter Flow more physiologic) ¯ peak flow and 3.) pt effort Resp failure 30-40 (low VT use); Concern if >40. Flow = more flow), 4) pressure rise time (¯ Rise Time ® Peak v 0.9 Flow), 5) pt effort ( effort ® peak flow) Pplat-PEEP: tidal stress (lung injury & mortality risk). Target Determined by set RR, Vt, & Flow Pattern (i.e. for any set I:E Determined by patient effort & flow termination (“Esens” – PDriving peak flow, Square (¯ Ti) & Ramp ( Ti); Normal Ti: 1-1.5s; see below “Breath Termination”) < 15 cmH2O. -
Pulse Oximetry Is Essential in Home Management of Elderly COVID-19 Patients Md
55 Bangladesh J Otorhinolaryngol 2020; 26(1): 55-67 Case Report Pulse Oximetry is Essential in Home Management of Elderly COVID-19 Patients Md. Abdullah Al Harun1, Mohammad Murad Hossain2, Mohammad Anwarul Bari3, Nazmul Ahsan Siddiqi Rubel4, Mohammad Enamul Karim5, Nadia Siddiquee6, Mohammad Delwar Hossain7, Farhana Sultana8, Ahmmad Taous9, AKM Monwarul Islam10, Salma Khatun11, AHM Afzalul Haque12, Mohammad Mahbub-Ul Haque13, KM Mamun Murshed14, Syed Atiqullah15, Abu Mohammad Ekramul Hoque16, Mohammad Abdullah17 Abstract Background: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) is in Pandemic form and has affected people of 215 countries. It produces symptoms like fever, cough, shortness of breath, sore throat, headache, loss of taste, smell or appetite and many other rare symptoms. But the most important symptom is shortness of breath due to hypoxia. In a normal individual oxygen saturation (SpO2) is at least 95% and patient feels shortness of breath when SpO2 falls below 90% with some exception. SARS-CoV-2, a newly emergent coronavirus has the peculiarity to produce silent hypoxia, meaning SpO2< 90% or less like 80%, 70%, 60% without shortness of breath. Silent hypoxia can be diagnosed by monitoring SpO2 with pulse oximeter. For management of COVID-19, early symptoms like fever & cough, SpO2 should be monitored by pulse oximeter, followed by immediate correction of hypoxia by O2 supplementation and prophylactic oral or injectable anticoagulant to prevent thromboembolism and thus death rate can be reduced. Case summary: A 72-year-old man presented with the complaints of fever and headache followed by cough, fatigue, anorexia, loss of taste and appetite in next few days but no shortness of breath. -
Pulmonary Surfactants and Their Role in Pathophysiology of Lung Disorders
Indian Journal of Experimental Biology Vol. 51, January 2013, pp. 5-22 Review Article Pulmonary surfactants and their role in pathophysiology of lung disorders Aparna Akella & Shripad B Deshpande* Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous- aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. It is essential for efficient exchange of gases and for maintaining the structural integrity of alveoli. Surfactant is a secretory product, composed of lipids and proteins. Phosphatidylcholine and phosphatidylglycerol are the major lipid constituents and SP-A, SP-B, SP-C, SP-D are four types of surfactant associated proteins. The lipid and protein components are synthesized separately and are packaged into the lamellar bodies in the AT-II cells. Lamellar bodies are the main organelle for the synthesis and metabolism of surfactants. The synthesis, secretion and recycling of the surfactant lipids and proteins is regulated by complex genetic and metabolic mechanisms. The lipid-protein interaction is very important for the structural organization of surfactant monolayer and its functioning. Alterations in surfactant homeostasis or biophysical properties can result in surfactant insufficiency which may be responsible for diseases like respiratory distress syndrome, lung proteinosis, interstitial lung diseases and chronic lung diseases. The biochemical, physiological, developmental and clinical aspects of pulmonary surfactant are presented in this article to understand the pathophysiological mechanisms of these diseases. -
Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis
International Journal of Molecular Sciences Review Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis Olga Cañadas 1,2,Bárbara Olmeda 1,2, Alejandro Alonso 1,2 and Jesús Pérez-Gil 1,2,* 1 Departament of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, 28040 Madrid, Spain; [email protected] (O.C.); [email protected] (B.O.); [email protected] (A.A.) 2 Research Institut “Hospital Doce de Octubre (imasdoce)”, 28040 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-913944994 Received: 9 May 2020; Accepted: 22 May 2020; Published: 25 May 2020 Abstract: Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface. Keywords: pulmonary surfactant film; surfactant metabolism; surface tension; respiratory air–liquid interface; inflammation; antimicrobial activity; apoptosis; efferocytosis; tissue repair 1. -
The Effect of Continuous Positive Airway Pressures on Lung Volumes
Paraplegia (1996) 34, 54- 58 © 1996 International Medical Society of Paraplegia All rights reserved 0031-1758/96 $12.00 The effect of continuous positive airway pressures on lung volumes in tetraplegic patients 2 LA Harveyl and ER Ellis 2 1 Physiotherapy Department, The Prince Henry Hospital, Sydney; School of Physiotherapy, Faculty of Health Sciences, The University of Sydney, Sydney, Australia Continuous positive airway pressure (CPAP) is widely advocated for the treatment of respiratory complications. However the effects of CPAP on the respiratory function of tetraplegic patients have not yet been investigated. The purpose of this study was to examine the effects of breathing with different levels of CPAP on the relationship between closing volume (CV) and functional residual capacity (FRC) in ten recently injured, but otherwise healthy tetraplegic patients with lesions between the fourth and eighth cervical segments. Lung volumes were measured before, during and after 32 min of zero end-expiratory pressure and 5 and 10 cm H20 of CPAP. FRC was measured by the open-circuit nitrogen washout method and CV was measured by the single breath nitrogen washout method. FRC was unaffected by zero end-expiratory pressure, but both 5 cm H20 and 10 cm H20 of CPAP caused significant increases in FRC. FRC returned to pre-CPAP values by the first minute after removal of 5 and 10 cm H20 of CPAP. We were unable to measure CVs in any subjects. It was concluded that 5 and 10 cm H20 of CPAP increase FRC in healthy tetraplegic individuals, but that these increases are rapidly lost with the subsequent removal of CPAP. -
Synthetic Surfactant with a Recombinant Surfactant Protein C Analogue Improves Lung Function and Attenuates Inflammation in a Mo
Zebialowicz Ahlström et al. Respiratory Research (2019) 20:245 https://doi.org/10.1186/s12931-019-1220-x RESEARCH Open Access Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits J. Zebialowicz Ahlström1†, F. Massaro2†, P. Mikolka1,3†, R. Feinstein4, G. Perchiazzi5, O. Basabe-Burgos1, T. Curstedt6, A. Larsson5, J. Johansson1 and A. Rising1,7* Abstract Aim: In acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS. Methods: ARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (VT 20 m/kg body weight) until P/F ratio < 26.7 kPa. The animals were treated with two intratracheal boluses of 2.5 mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf®), both surfactants containing 80 mg phospholipids/mL, or air as control. The animals were subsequently ventilated (VT 8–9 m/kg body weight) for an additional 3 h and lung function parameters were recorded.