RESPIRATORY FUNCTIONS MECHANICS OF RESPIRATORY SYSTEM GAS TRANSPORT RESPIRATORY SYSTEM Anat dých sys Kiss astma v bronších termBronchiol s alveolyLidské tělo STEPS IN THE DELIVERY OF O2 TO THE CELLS airways alveoli alveolar-capillary m. capillary UTILIZATION OF O2 BY MITOCHONDRIA TRANSPORT OF O2 IN THE BLOOD DIFFUSION OF O2 ACROSS ALVEOLAR-CAPILLARY MEMBRANE DIFFUSION OF O2 FROM CAPILLARY TO THE CELLS 1 VENTILATION OF THE LUNGS INTERNAL RESPIRATION CO2 OUTPUT ~250 ml / min O2 UPTAKE ~300 ml / min AT REST AIR PASSAGES ANATOMICAL DEAD SPACE –CONDUCTING ZONE NASAL PASSAGES PHARYNX LARYNX TRACHEA BRONCHI BRONCHIOLES TERMINAL BRONCHIOLES 2 RESPIRATORY ZONE (GAS EXCHANGE) Total alveolar area ~100 m2 Other physiological functions: air is warmed, cleaned and takes up water vapour respiratory reflex responses to the irritants speech and singing (function of larynx, vocal cords) Folie8 předb cut aa ciliated cylindrical epithelium lamina propria visceral pleura smooth muscle cells cartilage blood vessels gland goblet cell mucus 4 AUTONOMIC INNERVATION of smooth muscle cells Stimulation via parasympathetic NS - n.vagus due to Muscarinic receptors: Acetylcholine activates bronchoconstriction Stimulation via to sympathetic NS – due to catecholamins in circulation b2-adrenergic receptors: Noradrenaline activates bronchodilatation BRONCHUS Æ < 1 mm TERMINAL BRONCHIOLE řasinky dýchacích cest Cylindrical epithelium with cilia Picture: the idea of a seabed with sea anemones 6 IN HEALTHY INDIVIDUALS both spaces are practically identical DEAD SPACE TOTAL GAS VOLUME NOT EQUILIBRATED WITH BLOOD (without exchange of gasses) ANATOMICAL dead space - volume of air passages FUNCTIONAL (total) dead space ANATOMICAL dead space + total VOLUME of ALVEOLI without functional capillary bed f = 12/min VT = VA + VD VD part of tidal volume remaining in the dead space ~ 150 ml 5 4.2 l/min 6 l/min ALVEOLAR VENTILATION VA · = VA x f 1.8 l/min DEAD SPACE VENTILATION VD · = VD x f PULMONARY MINUTE VENTILATION V ∙ = VT x f VT tidal volume ~ 500 ml VA part of tidal volume entering alveoli ~ 350 ml DEAD SPACE – nitrogen test (force inspiration of pure O2, follow slowly expiration with monitoring of concentration of nitrogen) Folie10 před cut SPIROMETRY water seal subject inspiration expiration inverted bell 7 (measurements of lung volumes, capacities, functional investigations, …) pulley string Folie11 před cut bb LUNG VOLUMES TIDAL VOLUME VT EXPIRATORY RESERVE VOLUME ERV ~1.7 8 maximal inspiratory level RESIDUAL VOLUME RV ~1.3 maximal expiratory level end of quiet expiration DILUTION METHOD He INSPIRATORY RESERVE VOLUME IRV ~2.5 [l ] end of quiet inspiration He reservoir (Vr) RV ci 3 Calculation of residual volume RV from the initial and final He concentrations in reservoir (ci , cf). He reservoir (V) RV cf Þ Equilibration of the air in the residual volume and reservoir Principle of method: 1 Maximal expiration, 2 Repeated inspiration from and expiration into a reservoir (known volume Vr) with inert gas He (known concentration ci) Folie11 před cut bb maximal expiratory level maximal inspiratory level VC - the largest amount of air that can be expired after maximal inspiration VC VITAL CAPACITY = VT + IRV + ERV ~ 4.7 l VC 9 TLC TOTAL LUNG CAPACITY = VC + RV ~ 6.0 l TLC ~1.2 l RV FUNCTIONAL RESIDUAL CAPACITY <3.0 l end of quiet expiration INSPIRATORY CAPACITY >3.0 l FUNCTIONAL INVESTIGATION OF THE LUNGS TIMED VITAL CAPACITY (FEV1 - forced expiratory volume per 1 s) PULMONARY MINUTE VENTILATION RMV (respiratory minute volume) at rest (0.5 l x 12 breathes/min = 6 l/min) PEAK EXPIRATORY FLOW RATE (PEFR) (~10 l/s) MAXIMAL VOLUNTARY VENTILATION (MVV) (125-170 l/min) 10 V [l] Čas [s] 1 s FEV1 0 1 2 3 4 5 1 s V [l] Čas [s] 0 1 2 3 4 5 1 s V [l] Čas [s] Healthy people Obstruction disease FVC physiology values FVC physiology values FEV1=80% FEV1 lower than 70% Restriction disease FVC lower than physiology values FEV1 – as physiology value Flow – volume curve •PEF – peak expiratory flow •MEF – maximální maximal expiratory flow on the differential levels of FVC - 75 %, 50 % a 25 % FVC PEF MEF75% MEF50% MEF25% TLC IRV Vt ERV RV IRC VC FRC RV Tady jsem skončila PNEUMOGRAPHY Principle Pneumography – measurement of respiratory movements (via chest or abdomen) •respiratory belt (piesoelectrical principle – is the ability of crystal to generate of electrical voltage during its deformation) Record: •Resting breathing •Breathing after mild or intensive exercise •Evaluation of record –Ti, Te, BI a Am Am Ti Te BI PNEUMOTACHOGRAPHY Principle Pneumotachograph - the device consists of tubes of the same diameter arranged in parallel. One of the tubes has branches with tubes near both its ends (oral and external). These are connected to a pressure sensor that allows you to measure the differences in air pressure at the beginning and end of the pneumotachograph in proportion to the speed of the inhaled or exhaled air. •Mechanics of breathing Graf změny intrapleur tlaku Graf změny objemu Graf změny plícního tlaku Obrzměny intrapleur tlaku Silbernagl pulmonalis parietalis PLEURA FORCES PARTICIPATING IN RESPIRATION 12 QUIET RESPIRATION EXPIRATION - only passive (elastic) forces are in action INSPIRATION - active forces of inspiratory muscles prevail PASSIVE FORCES represented by: ACTIVE FORCES performed by respiratory muscles lungs elasticity chest elasticity obr 2a cut RESPIRATORY MUSCLES accessory muscles external intercostals diaphragm internal intercostals abdominal muscles EXPIRATORY INSPIRATORY 13 INSPIRATORY muscles QUIET breathing diaphragm (> 80 % ) external intercostals (< 20 % ) EXPIRATORY muscles 14 internal intercostals muscles of the anterior abdominal wall (abdominal recti, …) Only at FORCED breathing accessory inspiratory muscles (mm. scalene) FORCED breathing in addition dýchábí žebra Silbernagl dychani Hrudní košSilbernagl Bucket-handle and water-pump handle effects O2 20.98 % FO2 @ 0.21 N2 78.06 % FN2 @ 0.78 CO2 0.04 % FCO2 = 0.0004 Other constituents BAROMETRIC (ATMOSPHERIC) PRESSURE AT SEA LEVEL 1 atmosphere = 760 mm Hg PARTIAL PRESSURES OF GASSES IN DRY AIR AT SEA LEVEL PO2 = 760 x 0.21 = ~160 mm Hg PN2 = 760 x 0.78 = ~593 mm Hg PCO2 = 760 x 0.0004 = ~0.3 mm Hg 20 1 kPa = 7.5 mm Hg (torr) COMPOSITION OF DRY ATMOSPHERIC AIR obr 12 přech cut COMPOSITION OF ALVEOLAR AIR 760 mm Hg INSPIRED AIR EXPIRED AIR dead space O2 100.0 CO2 39.0 H2O 47.0 right heart left heart veins arteries periphery capillaries 21 760 mm Hg partial pressures in mm Hg 760 mm Hg N2 O2 158.8 CO2 0.3 N2 601.0 … O2 115.0 CO2 33.0 H2O 47.0 N2 564.0 … O2 95.0 CO2 41.0 H2O 47.0 N2 … … O2 40.0 CO2 45.0 H2O 47.0 N2 … … O2 40.0 CO2 45.0 H2O 47.0 N2 … … physiological shunts O2 100.0 CO2 39.0 ? ? obr 17 přech b cut obr 17 přech a cut HAEMOGLOBIN α α β β 1 nm Fe Fe N N N N N N N N DEOXY OXY N N N polypeptide chain polypeptide chain O2 Fe3+ (methaemoglobin) oxidation 25 fetal Hb γ γ Fe2+ tetramer porfyrin Hb4 + 4 O2 ↔ Hb4O8 oxygenation O2–HAEMOGLOBIN DISSOCIATION CURVE 100 50 PO2 (mm Hg) CO Hb 26 myoglobin fetal Hb 50 0 50 100 0 plateau area steep portion ↓ pH, ↑ CO2 ↑ BPG (2,3-bisphosphoglycerate) ↑ temperature methaemoglobin BOHR´S EFFECT (¯ pH, CO2) physiological range v a P50 physically dissolved O2 (1.4%) PCO (mm Hg) Simoid shape 16 P pressure r radius T surface tension LAW OF LAPLACE spherical structures EXPANSION OF ALVEOLI P1 > P2 P1 P2 COLLAPSE OF ALVEOLI - ATELECTASIS P r T r T P 2 = ? PATHOLOGY 17a SURFACTANT SURFACE TENSION LOWERING AGENT obr 5 přech ALVEOLAR EPITHELIAL CELLS macrofage fatty acids, choline, glycerol, amino acids, etc.) surfactant surfactant cycle exocytosis of lamellar bodies PHOSPHOLIPID dipalmitoyl fosfatidyl cholin TYPE II specialized granular epithelial cells PRODUCTION OF SURFACTANT TYPE I thin epithelial cells DIFFUSION OF GASSES EFFECT MAINLY IN THE EXPIRED POSITION obr 13 přech cut nucleus RED BLOOD CELL O2 O2 O2 Hb HbO2 CO2 CO2 CO2 ~1 µm 23 ALVEOLAR-CAPILLARY (RESPIRATORY) MEMBRANE ALVEOLAR-CAPILLARY (RESPIRATORY) MEMBRANE interstitial space ALVEOLAR AIR PO2 = 100 PCO2 = 39 (mm Hg) alveolar epithelial cell time interval of erythrocyte contact with respiratory membrane at rest 0.75 s PULMONARY CAPILLARY diameter about 5 µm nucleus capillary endothelial cell DIFFUSION OF GASES obr 16 přech cut PO2 PCO2 PO2 100 PCO2 40 mm Hg venous blood PO2 40 PCO2 46 mm Hg 40 100 60 80 mm Hg 24 time 0.75 s time interval of contact of erythrocyte with respiratory membrane at rest Δ PO2 @ 60 mm Hg Δ PCO2 @ 6 mm Hg equalization with alveolar pressures PO2 100 PCO2 40 mm Hg TIME COURSE OF CAPILLARY PO2 AND PCO2 DURING GRADUAL EQUILIBRATION WITH ALVEOLAR AIR END Control of ventilation https://sleep.sharepoint.com/siteimages/Chapter%203.png •Breathing is an automatic process that takes place unconsciously. Automaticity of breathing comes from regular (rhythmic) activity of groups of neurons anatomically localized in the medulla and its vicinity. •They can be divided into three main groups: • –dorsal respiratory group – placed bilaterally on the dorsal side of the medulla oblongata, only inspiratory neurons, sending axons to motoneurons of inspiratory muscles (diaphragm, external intercostal muscles; their activation=inspiration, their relaxation=expiration; participates on inspiration at rest and forced inspiration – –ventral respiratory group - located on the ventrolateral part of the medulla oblongata, the upper part: neurons whose axons of motor neurons activate the main and auxiliary inspiratory muscles; the lower part: expiratory neurons which innervate expiratory muscles (internal intercostal muscles). Neurons in this group operate only during forced inspiration and forced expiration. – –Pontine respiratory group - pneumotaxic center - dorsally placed on top of the pont, contributes to the frequency and depth of breathing; affects the activity of respiratory neurons in the medulla oblongata. Chemical factors affecting the respiratory center: •Central chemoreceptors -on the front side of the medulla -sensitive only to increase of arterial pCO2 (by increasing H+ ) - - - -Notice: -central chemoreceptor are stimulated by other types of acidosis (lactate acidosis, ketoacidosis) •Peripheral chemoreceptors •– located in the aortic and carotid bodies •-primarily sensitive to decrease in arterial pO2, particularly to decrease of O2 under 10-13 kPa in the arterial blood. •They convey their sensory information to the medulla via the vagus nerve and glossopharyngeal nerve. • •Mechanism of action: Decreased ATP production in mitochondria leads to depolarization of receptors membrane and to excitation of chemoreceptor http://www.medicine.mcgill.ca/physio/resp-web/sect8.htm, Modulation of respiratory output Major parameters for feedback control – classical gases:pO2, pCO2, pH In additin to these, the respiratory system receives input from two other major sources: 1. variety of stretch and chemical/irritant receptors that monitor the size of airways and the presence of noxious agentsreceptors in respiratory system 2. Higher CNS centers that modulate respiratory activity for the sake of nonrespiratory activities Irritants receptors on mucose of respiratory system – rapidly adapting Stimulus: agens - chemical substances (histamin, serotonin, prostaglandins, ammonia, cigarette smoke). Respons: increase mucus secretion, constriction of larynx and brochus C-fibre receptors (juxtacapillary=J receptors)– free nerve ending of n.vagus (unmyelinated axon) in intersticium of bronchus and alveolus; Stimulus: Mechanical irritans (pulmonary hypertension, pulmonary oedema)+chemical Response: hypopnoe, rapid shallow breathing, bronchoconstriction, cough Stretch receptors slowly adapting (mechanoreceptors in tracheobronchial tree that detect the changes in lung volume by sensing the stretch receptors of the airway wall), inform to brain about the lung volume to optimize respiratory; its irritants triggered decrese activity of respiratory centre – Hering-Breuer´s reflexes. (protecting the lungs from overinflation/deflation) Baroreceptors – suppresses activity of respiratory centre Irritants of proprioreceptors of muscles, tendons during active and pasive movements of limbs Influenced activity of respiratory neurons (increase minute ventilation during work load) Limbic system, hypothalamus – strong pain, emotion Tractus corticospinalis =cortex – activated RC during work load temperature • F:\FRVŠ\FILM FOTO FINAL\001.jpg • • 50 • Upraveno dle: Poopesko Peter a kol. (1990) • • 51 • • • TRACHEA N. VAGUS white thin string A. CAROTIS ENDOTRACHEAL CANNULA • • 52 HERING-BREUER REFLEX HB před vagotomií001 • REFLEX STOP BREATHING • ARTEFAKTS • ARTEFAKTS • • 53 VAGOTOMY klidové dých po vagotomii004 • • • • One-side VAGOTOMY Both-side VAGOTOMY inspirium exspirium Periodic breathing •It is not regular, rhythmic, but respiration occurs in periods ("a moment to breathe, take a moment to not breathe„) • •CHEYNE-STOKES •BIOT‘S •„gasping“ •KUSSMAUL Christmas custom – cutting an apple - asterisk means health and happiness for the New Year Merry Christmas and Happy New Year 2022 Hypoxia, hypoxemia •Hypoxia is a general name for a lack of oxygen in the body or individual tissues. •Hypoxemia is lack of oxygen in arterial blood. •Complete lack of oxygen is known as anoxia. The most common types of hypoxia: 1.Hypoxic - physiological: stay at higher altitudes, pathological: hypoventilation during lung or neuromuscular diseases 2.Transport (anemic) - reduced transport capacity of blood for oxygen (anemia, blood loss, CO poisoning) 3.Ischemic (stagnation) - restricted blood flow to tissue (heart failure, shock states, obstruction of an artery) 4.Histotoxic - cells are unable to utilize oxygen (cyanide poisoning - damage to the respiratory chain) OXYGEN FALL mmHg dry atmospheric air 159 humid atmospheric air 149 ideal alveolar gass 105 end-expiration air 105 arterial blood 77 cytoplasma – mitochondria 3-10 mixed venous blood 40 venous blood 20 S02401-002-f007 pO2 = 1 mmHg Hypercapnia • Hypercapnia - increase of concentration of carbon dioxide in the blood or in tissues that is caused by retention of CO2 in the body • possible causes: total alveolar hypoventilation (decreased respiration or extension of dead space) • mild hypercapnia (5 -7 kPa) causes stimulation of the respiratory center (therapeutic use: pneumoxid = mixture of oxygen + 2-5% CO2) • hypercapnia around 10 kPa - CO2 narcosis - respiratory depression (preceded by headache, confusion, disorientation, a feeling of breathlessness) •hypercapnia over 12 kPa - significant respiratory depression - coma and death. Travelling by aircraft (On board aicraft is pressure as on 2000 m above see level) High risk for patients with diseases: - concentration of hemoglobin lower than 60 % - severe step of atherosclerosis - cardial insuficiency - respiratory insuficiency - non-treated hypertension (BP ower 200/100mmHg) Toxicity of oxygen The toxicity seems to be due to the production of the superoxid anion and H2O2 Causes: - lost of possibility binding CO2 in venous blood - in lungs – pulmonary edoema – decrease CO2 expenditure Critical values > 40 kPa (300 mmHg) –dependence on time Toxicity of oxygen Exposure – 8 hours:- respiratory passages became irritated - Substernal distress - Nasal congestion - Sore throat - Cough - 24-48 hours: - damage of lungs – decrease production of surfactant Recommendation: 100 % - give discontinuosly THANK YOU FOR YOUR ATTENTION C:\Documents and Settings\ja2\Dokumenty\Obrázky\bílé vánoce.jpg obr 19 přech cut TRANSPORT OF CO2 Cl- HAMBURGER CHLORIDE SHIFT H2 CO3 CO2 + H2O CA CA – carbonic anhydrase H2O 27 HCO3- H+ + H+ + deoxyHb- H-deoxyHb HCO3- Cl- CO2 obr 20 přech b cut obr 20 přech a cut HbO2 CO2 O2 28 CO2 CO2 CO2 physically dissolved (~5.3%) CO2 O2 Cl- HCO3- CO2+ H2O HCO3- + H+ CO2 + H 2O HCO3- + H+ (~89%) Hb.CO2 CO2 + Hb-NH2 Hb.NH-COO- (carbamino-Hb) (~5.3 %) 60% in plasma, 29% in red blood cell obr 21 přech copy HALDANE EFFECT CO2 DISSOCIATION CURVE deoxygenated blood 5 10 15 20 25 30 10 20 30 40 50 60 70 PCO2 (mm Hg) physically dissolved CO2 a v oxygenated blood 29 deoxygenated blood in peripheral tissues oxygenated blood in the lungs CO2 + H2O H2CO3 H+ + HCO3- Hb- + H+ HHb TISSUES: DEOXY-Hb binds H+ more readily (weaker acid) Þ ↑ amount of chemically bound CO2 ? physiological values in arterial and venous blood Hb.NH.COO- 1 Hb- + H+ HHb 2 LUNGS: H+ is released from OXY-Hb Þ ↓ amount of chemically bound CO2 DEOXY-Hb I PHYSIOLOGY OF AIR PASSAGES II BASIC MEASURABLE PARAMETERS IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE III ACTIVE AND PASSIVE FORCES VI TRANSPORT OF O2 AND CO2 IN THE BLOOD I AIR PASSAGES II MEASURABLE PARAMETERS LUNG VOLUMES FUNCTIONAL INVESTIGATION CHARACTERISTIC PRESSURES · · · · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING III ACTIVE AND PASSIVE FORCES · · · · VI TRANSPORT OF GASSES (O2 and CO2) Folie17 přech a cut 3 Folie17 přech a cut 1 Folie17 přech a cut 2 VT [l] time -3 -6 [mm Hg] [mm Hg] +1 -1 11 P.V = const PA ALVEOLAR (INTRAPULMONARY, LUNG) PA PPL INTRAPLEURAL (INTRATHORACIC) PPL TIME COURSE OF PRESSURES AT QUIET RESPIRATION INSPIRATION EXPIRATION PA < PATM PA > PATM measured curve theoretical curve ? ? 1 kPa = 7.5 mm Hg LUNGS ELASTICITY INHERENT TISSUE ELASTICITY (elastin and collagen fibres) SURFACE TENSION FORCES air-liquid interface in alveoli 15 obr 3 přech 200 150 100 50 0 0.4 ALVEOLAR PRESSURE (kPa) 0.8 1.2 1.6 2.0 HYSTERESIS LOOP INFLATION DEFLATION opening pressure AIR LUNGS ELASTICITY SALINE 200 150 100 50 0 0.4 ALVEOLAR PRESSURE (kPa) 0.8 1.2 1.6 2.0 HYSTERESIS LOOP INFLATION DEFLATION opening pressure AIR SALINE Factors involved in HYSTERESIS LOOP 17b LAPLACE LAW (responsible for high opening pressure of alveoli) Dynamic changes in the DENSITY of surfactant molecules during INSPIRATION and EXPIRATION obr 6 přech b cut COMPLIANCE (VOLUME STRETCHABILITY) alveolar pressure DPA (mm Hg) 0 100 50 150 200 -50 -100 0 +1 -1 +2 +3 -2 VC RV FRC relaxation volume 18 relaxation pressure curve STATIC MEASUREMENT IN CLOSED SYSTEM V P DP DV compliance is increased ¯ stiffness of the tissue compliance is decreased stiffness of the tissue P V C D D = end of quiet expiration Valsalva maneuver Müller´s maneuver TOTAL RESPIRATORY SYSTEM (lungs and chest) ELASTIC (STATIC) WORK to overcome the elastic forces of the chest and lungs DYNAMIC WORK to overcome the resistance of air passages during the air movement – AERODYNAMIC RESISTANCE (~ 28%) to overcome the friction during mutual movement of inelastic tissues – VISCOUS RESISTANCE (~ 7%) 19 TOTAL WORK OF RESPIRATORY MUSCLES AT QUIET BREATHING (65%) (35%) I AIR PASSAGES II MEASURABLE PARAMETERS LUNG VOLUMES FUNCTIONAL INVESTIGATION CHARACTERISTIC PRESSURES · · · · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING III ACTIVE AND PASSIVE FORCES · · · · VI TRANSPORT OF GASSES (O2 and CO2) Alveolar PO2 and PCO2 at voluntary hypo- and hyperventilation 22 50 100 2 4 6 8 10 alveolar ventilation (l/min) PAO2 hyperventilation → hypocapnia → respiratory alkalosis hyperventilation hypoventilation → hypercapnia → respiratory acidosis hypoventilation PACO2 0 0 At QUIET RESPIRATION composition of alveolar air remains constant (functional residual capacity ~3.0 l)