Lecture. Key concepts

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1 Dr.Puntarica Suwanprathes Physiology Department Faculty of Medicine Siriraj Hospital Mahidol University 1 2 version 2005 Lecture 1. Basic principle 2. Mechanic of breathing (x2) 3. Lung volume 4. Pulmonary circulation 5. Control of ventilation (x2) 6. Blood gas diffusion Blood gas and ph (Yr III) (Total: 11 hrs +1 hr) Name: ป ณฑร กา ส วรรณประเทศ office: ต กจ ฑาธ ช 1 7. Blood gas transport Tel: ext: Metabolism 4 Key concepts กระบวนการท างานของระบบหายใจ หล กการทางฟ ส กส ในสร รว ทยาระบบหายใจ โครงสร างของปอด โครงสร างของทรวงอก หน าท อ นๆ ของปอด 5 6

2 ENERGY chemical reaction O 2 chemical reaction metabolism (conversion of energy forms) 7 CO 2 ENERGY 8 Multi-cellular organism simple diffusion cell membrane unicellular organism 9 10 evolution supply O 2 get rid of CO

3 MATCHING Ventilation Blood flow Air pump supply get rid of Ventilation-perfusion ratio V/Q ratio = 0.8 Blood pump Breathing or Respiration In general: Physiology: External Respiration Transport mechanism Internal Respiration 15 p.456 Respiration processes breathing external respiration pulmonary ventilation diffusion blood-gas tansportation diffusion internal respiration or cellular respiration 16 get rid of CO2 supply O 2 PaO 2 = 100 mm.hg PaCO 2 =40mm.Hg Partial Pressure of Gas Gas % pressure or tension Unit: mmhg ABG 17 18

4 Left ventricle reservoir Biochemical reaction Gas exchange Filtration Air conditioning 19 Airway defense mechanism 20 Respiratory Structure Ventilation Diffusion Perfusion 21 URI Upper respiratory tract nasal cavity trachea Lower respiratory tract lower part of trachea main bronchai + lungs Thoracic cavity 22 Respiratory Structure 2 zones 1. Conducting zone 2. Respiratory zone 23 Structures of the lungs Respiratory tract airways 23 generations Weibel conducting zone anatomical dead space 16 generations Respiratory zone respiratory unit acinus 7 generations 24

5 Pharynx Nasal cavity nose Trachea Nostril Larynx terminal bronchioles Right lung Left lung No gas exchange acinus 5 mm Anatomical dead space 25 ~ μ 26 Trachea wind pipe Tracheal rings: C-shaped, cartilagenous rings (keep trachea open) Bronchus (primary, 1 O ) first branch off the trachea similar in structure to the trachea smaller bronchi, less cartilage Bronchioles *** no cartilage smooth muscles dominates lumen diameter is regulated by the ANS Sympth: diameter Parasymp: diameter 27 Right Lungs Left: 2 lobes Cardiac notch. Right: 3 lobes Left are made of collections of 2 O bronchi and 3 O bronchi, bronchioles, alveoli and other structures 28 Alveoli respiratory bronchioles alveolar ducts alveolar sacs alveoli gas exchange 5 mm million (30 million 2-3 yrs 8 yrs) diameter ~ μ surface area m 2 (40 times more than BSA: body surface area) 30

6 Alveolus Types 2 pneumocytes Types 1 pneumocytes interstital fluid alveolar fluid lining with pulmonary surfactant macrophages Alveolar capillary membrane alveolus 0.2 μ Alveolar capillary membrane Alveolar epithelium Type I: alveolar epithelial cell or squamous pneumocytes μ thick about 90% of alveolar surface plays a role in gas exchange Type II: alveolar epithelial cell or granular pneumocyte secrete surfactant, which reduce the surface tension assist pulmonary extension in respiration. macrophage or dust cell phagocytoses airborne particles, microorganisms and pulmonary cell debris and keep the alveolar surface clean 33 Left ventricle reservoir Filtration Biochemical reaction Air conditioning Airway defense mechanism 34 Air conditioning Filtration warming moisturizing filtering nose, nasal turbinate: particles > 10 μm nasopharynx-larynx: particles < 10 μm trachea, bronchi: particles 2-10 μm alveolar duct, alveoli: particles μm expired air: particles < 0.5 μm 35 36

7 mucous membrane covered with cilia Filtration hair dust particles eddy current Turbulent precipitation mucus Turbulent precipitation mucus Terminal bronchioles ciliated nasal septum epithelial ciliary escalator turbinates membranes pharyngeal wall Airway defense mechanisms Airway defense mechanisms Lungs the largest surface area of the body in contact with the environment Mucocilliary transport susceptible to damage by foreign materials dust particles pollen airborne pollutants gateway for infection bacteria viruses fungal spores 39 Phagocytic macrophage 40 Mucocilliary transport cells with microvilli 2 - ciliated cells ciliated cells beat at 20 cycle/sec mucociliated escalator mm/min (in small airways) 5-20 mm/min (in trachea and main bronchi) paralysis of cilia from noxious agents (eg. sulphur dioxide, ) smoke cold air many drugs (eg. general anaesthetics) 41 dust particle gel layer sol layer mucus mucus gland globlet cell 42

8 Phagocytic macrophage macrophage phagocytic macrophages dust cells dust particles bacteria debris etc. ingest and transport to Bronchioles mucocilliary clearance Lymphatic system or CVS 43 high density of blood supply nose nasopharynx Warming nasal cavity nasal septum turbinates Humidification lower trachea Air temp. close to body temp. 44 Key concepts 1) physic of gases 2) partial pressure of gases 3) lung volumes and capacities 4) minute ventilation and alveolar ventilation PACO 2 5) alveolar ventilation 45 PAO 2 46 Physics of gases gas gas particles are always in motion random movement travel in straight lines unless they collide other particles or the walls of the container pressure 47 48

9 Boyle s law gas particles temp pressure volume 49 temp.: constant volume = constant pressure 50 Charles's Law pressure: constant volume = constant x temperature 51 absolute (Kelvin) degree (273 o K= 0 o C) volume: constant pressure = constant x temperature 52 Gas Law Boyle s law + Charles s law pressure, volume, temperature PV = nrt PV = nr = constant T P 1 V 1 = P 2 V 2 T 1 T 2 n = mols R = gas constant R = mmhg-l/k-mol) P = mm.hg V =L T = Kelvin 53 Partial Pressure of Gas Gas % pressure or tension Unit: mmhg 54

10 Dalton s law of partial pressure Partial Pressure of Gas P A P B P C Definition:. each gas Partial Pressure of Gas P A P B P C gas mixture (A+ B +C) total gas pressure (Ptot) gas mixture gas A gas B gas C partial pressure of gas X (Px) partial pressure or tension % or concentration of gas X 55 gas mixture gas A gas B gas C PA PB PC = PA + PB + PC e.g. (50%) (30%) (20%) Ptot = 100 mmhg Ptot = 200 mmhg Ptot = 760 mmhg 56 Ptot = 760 mmhg Atmospheric pressure (P B ) or 1 ATP Partial Pressure of Gas gas mixture gas A gas B gas C 50% 30% 20% if Ptot = 100 mmhg if Ptot = 760 mmhg Px = Ptot. Fx Fx PC = 20 mmhg PC = 20 x fractional concentration of gas x 57 gas A PA gas B gas C + + = PB PC gas mixture (A+ B +C) PA + PB + PC Px = Ptot. Fx < 1 Px = partial pressure P = total dry gas pressure Fx = fractional concentration of gas x X% The vapor pressure of water sea level water Gas saturated with water vapor H 2 O H 2 O H 2 O Atmospheric pressure (P B ) = 760 mm.hg (1 ATP) Total pressure = summation of partial pressure of each gases PB = PO 2 + PCO 2 + PN 2 + PH 2 O vapor pressure H 2 O of water 59 60

11 humidified air PB = PO 2 + PCO 2 + PN 2 + PH 2 O Temp.? water vapor partial pressure 37 o 37 0 C, PH 2 O = C, PH 2 O = C, PH 2 O = 30 mmhg water vapor at body temperature = 47 mm.hg 61 ***Body 37 0 C, PH 2 O = 47 mmhg PO 2 + PCO 2 + PN 2 = PB - 47 = 713 mmhg 62 dry gas Px = (760 47) Fx e.g. alveolar air (% of dry gas) O 2 = 14% CO 2 = 5.6% N 2 = 80.4% e.g. PACO2 = PAO 2 = (760-47) x 5.6 ~ 40 mm.hg 100 (760-47) x 14 ~ 100 mm.hg Pulmonary Function Test Spirometer PFT Spirometer Spirometry Spirogram Volume-displacement spirometer displacement of the bell etc. * Flow-sensing spirometer 65 66

12 Volume-displacement spirometer mid-twentieth century based on the simple mechanical principle.air, exhale from the lung, will cause displacement of a closed chamber that is partially submerged in water 67 counterbalance cylinder water pen weight Rotating drum inspiration 68 Flow-sensing spirometer Pulmonary capacities Pulmonary volume add water 400 ml ml. capacities volume B add water 600 ml. volume A Lung volumes Spirogram Pulmonary volumes (500 ml) Tidal Volume (3000 ml) Inspiratory Reserve Volume (1100 ml) Expiratory Reserve Volume (1200 ml) Residual Volume Pulmonary capacities Inspiratory Capacity Vital Capacity Functional Residual Capacity Total Lung Capacity (resting expiration level) 71 volumes capacities 72

13 Residual Volume B A Expiratory Reserve Volume Tidal volume Inspiratory Reserve Volume resting expiration level ventilation rest, Tidal volume ~ 500 ml. (TV or V T ) 350 ml. 150 ml. alveoli alveolar air conducting airways anatomical dead space 75 (V D ) Dead space Definition:... 3 types: Anatomical dead space, VD 2. Alveolar dead space 3. Physiological dead space 76 Anatomical dead space Alveolar dead space No gas exchange dead space or Dead space volume ~ 150 ml Alveolar dead space diffusion no diffusion gas exchange Alveolar volume or Alveolar air ~ 350 ml 77 Causes: no blood flow blood flow (uneven V/Q) *** note: in normal lungs very small!!! 78

14 Physiological dead space Anatomical dead space Alveolar dead space*** Minutes Ventilation VT Minute Volume MV or Minute Ventilation V T definition:.. MV = TV x RR Unit: Liter / minute V T = V T x RR Respiratory Minute Volume Minute Volume MV 81 at rest: TV ~ 500 ml RR ~ count / minute MV ~ 6000 ml (6 L) to 10,000ml (10 L) 82 Alveolar Ventilation Alveolar Ventilation No gas exchange VA definition:.. dead space or Dead space volume ~ 150 ml Unit: Liter / minute gas exchange Alveolar air 83 Alveolar volume or Alveolar air ~ 350 ml 84

15 Alveolar Ventilation VA V A = (V T - V D ) x RR = ( ) x 12 (or x 20) = 4,200 ml/min (or 7,000 ml/min) = 4.2 L/min (or 7 L/min ) CO 2 O 2 V A ~ 3-7L,average = 5L VA ~ 70% VT Respired air end-tidal sample 14% 5.6% inspired air 20.94% 0.04% alveolar air expired air 16.3% 4.5% dead space air alveolar air %O 2 VD PACO 2 PACO 2 VECO 2 %CO VA VT = PACO 2 - PECO 2 PACO 2 VD VT = PACO 2 - PECO 2 PACO 2 (~ mmhg) FECO 2 x VT = (FICO 2 x VD) + (FACO 2 x VA) C R %CO 2 expired air inspired air 4.5% 0.04% TV = 450 ml alveolar air 5.6% 89 Anatomical dead space VD ~ 150 ml 90

16 PACO 2 VECO 2 VA constant Abnormal in Alveolar Ventilation If VA Alveolar hypoventilation Alveolar hyperventilation hyperventilation PaCO 2 PaCO 2 If VA hypoventilation Key concepts 2 circulation 1) pulmonary circulation compare with systemic circulation 2) pulmonary vascular resistance (PVR) Bronchial circulation 3) passive and active changes of PVR 4) ventilation-perfusion ratio Alveoli 95 Pulmonary circulation 96

17 deoxygenated blood mixed venous blood 3cm, length 5 cm Pulmonary artery Pulmonary circulation *** Alveolar capillaries Systemic circulation Bronchial circulation oxygenated blood Bronchial artery Function Pulmonary circulation SYSTEM Right lung vessels 1) Reservior 5 parts working system 2) Pump Upper body vessels 3) Distributing system pulm. artery (150 ml) Left lung vessels 4) Exchange system pulm. capillaries bed (~75 ml) =SV p.510 Tracheobronchial tree 97 Lower body vessels Note: pulmonary blood volume ~500 ml 5) Collecting system pulm. venules vein (270 ml) 98 Pulmonary circulation Pulmonary artery 24/9 (mean=14) Pulmonary capillaries Pulmonary vein Pulmonary circulation low pressure *** System circulation 100 1/7 Systemic vein /0 120/ Systemic circulation Systemic artery (Aorta) 120/80 (mean=100) 2 14 pulm. capillaries bed 10 5 Unit: mmhg 99 Systemic capillaries p.510 Unit: mmhg 100 Pulmonary circulation Pulmonary circulation Outer layer thinner smooth muscle Elastic white fibrous tissue Lesser circulation Endothelial cells Physiological functions Gas exchange Filter Blood reservoir for left ventricle Supply nutrients to lung itself Fluid exchange low pressure Angiotensin converting enzyme low resistance low vasomotor tone highly distensible

18 Exchange system diffusion area diffusion distance pulm. capillaries bed pulmonary capillaries bed network oriented thin-film coated look (thick ~ 0.1 μ) total exchanging areas ~ 70m 2 (40 times BSA) 103 pulm. capillaries pressure if pressure e.g. Lt. ventricle failure Pulmonary congestion H 2 O Lung compliance plasma protein < colloidal osmotic pressure (25 mmhg) 104 Pulmonary circulation Pulmonary capillaries Unit: mmhg Ohm s law: Resistance = Driving pressure Blood flow vascular resistance = pulm. arterial pr. left atrium pr. PVR = PPA - PLA Q 6 L/min Blood flow mm.hg L/min cardiac output 105 PVR = Pulmonary artery 24/9 (mean= 14) PPA - PLA Q Systemic vein PVR = = C.O. = 1 mmhg/l/min / /0 Systemic capillaries 9 30 Pulmonary vein Systemic circulation Systemic artery (Aorta) 120/80 (mean= 100) R = = 16.6 mmhg/l/min 106 Pulmonary circulation: 1 mmhg/l/min 0.06 mmhg/ml/sec Resistance ~ 0.06 mmhg ml/sec Systemic circulation: 16.6 mmhg/l/min mmhg/ml/sec Resistance ~ 1 mmhg ml/sec 16 times 107 Pulmonary vascular resistance Alternation of pulmonary vascular resistance 1. Passive change (change in environment) pulmonary blood flow lung volume (during inspiration- expiration) 2. Active change Hypoxia PACO 2 pressure in Lt. Atrium chemicals 108

19 Passive change Pulmonary blood flow rest collapse normal blood flow: 5-6 L/min during exercise blood flow e.g. exercise PVR = PPA - PLA Q dilate blood flow l/min or more BUT PVR slightly 109 recruitment distension 110 Passive change Passive change pulmonary arterial or venous pressure recruitment Pulmonary vascular resistance distension Lung volume normal CO CO p Pulmonary blood vessel location alveolar vessels extra-alveolar vessels alveolar vessels Alveolar vessels capillaries small arterioles venules extra-alveolar vessels Factor: Intrapleural pressure Extra-alveolar vessels capillaries *** small arterioles small venules pulmonary arteries pulmonary veins capillaries Pulmonary arteries Pulmonary veins corner vessels corner vessels Factor: Lung volume

20 capillary alveolar vessels extra-alveolar vessels Alveolar vessels capillaries small arterioles venules Factor: Intrapleural pressure Extra-alveolar vessels Pulmonary arteries Pulmonary veins inspiration lung volume vessels are compressed R capillaries Breath in expiration lung volume vessels distend R 115 Factor: Lung volume distend more - pr. 116 Pulmonary vascular resistance over all Effects of lung volume on pulmonary vascular resistance *** alveolar vessels extra-alveolar vessels *** FRC Active change Local Hypoxia Active change Hypoxemia ventilation PAO 2 Systemic Hypoxia PaO 2 (eg. High altitude) arteriolar constriction local HYPOXIA H + local response arteriolar constriction resistance O 2 pulm. vasoconstriction recruitment resistance..to e V/Q ratio Pulmonary arterial pressure shift blood 119 if chronic: pulmonary hypertension 120

21 Ventilation-Perfusion Relationships Ventilation-Perfusion Relationships Ideal lung 121 Factor 2: Rate? Blood flow concentartion = V/Q (gm/l) alveolar ventilation Model: 1 lung unit Factor 1: Rate? V (gm/min) con n Diffusion con n 122 Ventilation-Perfusion Relationships concentration = V/Q (gm/l) O 2 concentration in any lung unit (or PO 2 ) = ventilation blood flow Normal V/Q ratio PaO 2 = 100 mmhg PaCO 2 = 40 mmhg Ventilation-perfusion ratio V/Q ratio 123 Decreasing V/Q ratio Increasing V/Q ratio 124 V/Q ratio V/Q ratio alveolar PO 2 & PCO 2 arterial blood ventilation blood flow = 4 L/min = L/min In rest: O 2 consumption = 250 ml/min CO 2 production = 200 ml/min ventilation blood flow = 4 L/min = L/min rate 4 L/min matching If: V/Q ratio change? mismatch or uneven matching abnormal of Gas exchange air blood rate 5 L/min 125 PaO 2 & PaCO 2 126

22 Distribution of Distribution of Distribution of p.519 gravity Distribution of non-uniform distribution apex gravity Distribution of non-uniform distribution gravity 30 cm vary in hydrostatic pressure base > apex apex vary in hydrostatic pressure base > apex base 30 cm.h 2 O or 23 mm.hg 30 cm 30 cm.h 2 O or 23 mm.hg effect to regional blood flow *** blood flow to base > apex 129 base effect to regional blood flow *** blood flow to base > apex cm.H 2 O Distribution of apex non-uniform distribution gravity (wt.) vary in intrapleural pressure base (- pr.) < apex -10cm.H 2 O Distribution of apex 30 cm non-uniform distribution gravity (wt.) vary in intrapleural pressure base (- pr.) < apex 30 FRC: intrapleural pressure Base: -2.5cm.H 2 O apex: -10cm.H 2 O cm.h 2 O base initial base< cm.h 2 O FRC: intrapleural pressure Base: -2.5cm.H 2 O apex: -10cm.H 2 O initial base < apex when inspiration: *** ventilation to Base > Apex 131 when inspiration: *** ventilation to base > apex 132

23 slope p.521 *** higher C L more steep A2 B2 B1 = A1 volume *** V P V P higher C L more steep p Distribution of Distribution FRC: intrapleural pressure apex: -10cm.H 2 O base: cm.h 2 O less - cm.h 2 O FRC: intrapleural pressure apex: -10cm.H 2 O base: cm.h 2 O less - cm.h 2 O RV: intrapleural pressure apex: less negative base: + cm.h 2 RV: intrapleural pressure apex: less negative 30 cm base: + cm.h 2 O + cm.h 2 O base 30 cm small airways collapse!!! dynamic compression of airway *** when inspiration: *** ventilation to Apex > Base cm.h 2 O base small airways collapse!!! dynamic compression of airway *** when inspiration: *** ventilation to apex > base 136 Distribution of gravity perfusion: lesser apex transmural pr. alveoli: dilate zone 1 higher V/Q ratio press capillaries ventilation > perfusion dead space like effect lower V/Q ratio zone 2 zone 3 gravity ventilation = perfusion perfusion: greater arterial blood pr. Distribution of ***ventilation 1/3 blood flow 0.6 press alveoli base ventilation < perfusion venous-admixture effect or shut like effect 137 Base Apex 138 p.523 p.520

24 p Key concepts 1) Fick s law of diffusion 2) factors which limit gas transfer 3) diffusion capacity gas gaseous phase dissolved gas exert pressure*** equilibrium volume of dissolved gas partial pressure solubility 142 Graham s law diffusion rate or diffusion constant (D) = solubility Gaseous medium Liquid medium Gaseous medium MW CO 2 diffusion rate O 2 diffusion rate 5.6 = x = CO 2 diffusion rate O 2 diffusion rate = MW O 2 MW CO 2 = = Liquid medium CO 2 solubility O 2 solubility = = CO 2 diffusion rate faster than O 2 20 times 144

25 Solubility of Gas Henry s law CO 2 =PO 2. αo 2 CO 2 : concentration of O 2 (ml. O 2 /ml. solution) PO 2 : partial pressure or tension of O 2 (mm.hg) αo 2 : solubility coefficient of O 2 (ml. O 2 in 1 ml. solution / 1 ATP) 37 0 C : αo 2 = αco 2 = diffuse faster 145 equilibrium dissolved gas Low pressure equilibrium Low concentration Double the pressure equilibrium Double the concentration volume = partial pressure x solubility coefficient of dissolved gas (solubility) or concentration in solution 146 volume = partial pressure x solubility coefficient of dissolved gas or concentration constant in solution Diffusion concentration gas X in A > B Pressure gradient volume α partial pressure of that gas of dissolved gas A B gas mixture (A+ B +C) PA + PB + PC independence 147 partial pressure A > B diffuse from A to equilibrium A = B 148 Gas diffusion in Lungs PACO 2 40 mmhg PAO mmhg Duffusion rate: in gaseous medium Duffusion rate: in liquid medium PVCO 2 46 mmhg FACTORS: Diffusion rate Diffusion capacities PVO 2 40 mmhg

26 in gaseous medium diffusion rate: faster Graham s law Diffusion rate molecular wt.: lighter diffusion rate α 1 square root of density CO 2 diffusion rate = molecular wt. of O 2 alveolar duct diffusion distance ~1 mm alveolar-capillary interface O 2 diffusion rate molecular wt. of CO 2 = 32 = almost complete in sec. (80%) 152 Diffusion rate in liquid medium solubility pressure gradient or concentration gradient Henry s law volume α partial pressure of that gas of dissolved gas diffusion rate α solubility Diffusion rate O 2 > CO 2 in gaseous medium Graham s law CO 2 > O 2 in liquid medium Henry s law CO 2 diffusion rate = = 24.3 O 2 diffusion rate CO 2 diffusion rate = 5.6 x = 20.6 O 2 diffusion rate 6.6 x FACTORS: Diffusion rate Fick s law (Law of diffusion) V gas α A. D. (P 1 -P 2 ) T solubility MW V = diffusion rate A = area of diffusion D = diffusion constant T = length of diffusion path P 1 -P 2 = difference in partial pressure 155 Pressure difference across membrane difference in partial pressure alveoli pulm. capillary blood A diffusion rate time in pulmonary capillary = 0.75 sec. diffusion time = 0.25 sec. during exercise??? B 75 ml = 6 L/min pulm. blood flow 156

27 PvO 2 40 mmhg PvCO 2 45 mmhg O 2 CO 2 equilibrium PaO mmhg PaCO 2 40 mmhg PaO 2.. sec normal alveolar-capillary block severe Hypoxemia mixed venous PO Diffusion capacities Diffusion capacities diffusion P: 1 mmhg V (ml) time: 1 min alveolar-capillary membrane O 2 Gas volume: ml time: 1 min pr. gradient: 1 mmhg ml/min/mmhg 159 alveolar-capillary membrane 160 Diffusion capacities V gas α A. D. (P 1 -P 2 ) T can not measure V gas = D L. (P 1 -P 2 ) D L = V gas P 1 - P 2 Diffusion capacities mean P of capillary gas Diffusion capacities Measuring: Diffusion capacities O 2 CO DO 2 DcO Affinity: Single-breath method CO = 0.3% 1 breath: TLC breath-holding: 10 sec mean P of alveolar gas 161 exhale completely 162

28 Diffusion capacities DL = V gas P 1 -P 2 DO 2 exercise DCO = V CO P A CO -P C CO DO 2 = DCO x 1.23 DO 2 Normal value: DCO = 25 ml/min/mmhg DO 2 = 31 ml/min/mmhg 163 aging pulm. edema pulm. emphysema 164 Impaired diffusion! arterial blood gas tension? mild. rest exercise alveoli PaO 2 PaCO Light micrograph 166 Key concepts 1) O 2 and CO 2 transport in blood 2) Oxyhemoglobin dissociation curve 3) P50 4) O 2 capacity 5) O 2 content (CaO 2 or CvO 2 ) 6) %saturation of Hb with O 2 (%SaO 2 ) 7) O 2 delivery (DaO 2 ) 8) O 2 consumption (VO 2 ) 9) O 2 extract! 10) CO 2 production (VCO 2 )

29 Gas transportation CaO 2 PaO 2 O 2 capacity transport of O 2 CO 2 %SaO 2 CvO 2 VCO 2 DaO 2 VO2 2 Q CaO 2 loading Dissolved in plasma dissolved O 2 2. Combination with Hemoglobin Oxyhemoglobin 171 Dissolved in plasma 3% Henry s law volume α partial pressure of that gas of dissolved gas blood 100 ml PO 2 1 mmhg dissolved O ml Po 2 in arterial blood = 100 mmhg dissolved O 2 = 0.3 ml / 100 ml.blood 172 dissolved O 2 = 0.3 ml/ 100 ml.blood O 2 consumption (at rest) = 250 ml/min Combination with Hemoglobin 97% O 2 Hemoglobin (Hb) Oxyhemoglobin If use only dissolved O 2..? cardiac output = 250 x 100 ml/min = 83.3 L/min 0.3 BUT cardiac output (at rest) = 5-6 L/min 173 Hb + O 2 HbO 2 reversible reaction total O 2 carrying capacity times 174

30 Hemoglobin 4 polypeptide chains or subunit Globin protein saturation Hemoglobin Hb + O 2 HbO 2 reversible reaction deoxyhemoglobin (reduced Hb) oxyhemoglobin Heme (iron-porphyrin compound) Hb 4 +4O 2 Hb 4 O 8 conjugated protein 1Hbmolecule = 4 subunits Heme O oxygenation (0.01 sec.) 176 Hemoglobin Gas transportation in blood saturation Hb + O 2 HbO 2 reversible reaction O 2 oxygenation Hb 4 + O 2 Hb 4 O 2 Hb 4 + O 2 Hb 4 O 4 Hb 4 + O 2 Hb 4 O 6 Hb 4 + O 2 Hb 4 O 8 dissolved O 2 /CO 2 exert pressure Binding O 2 /CO 2 (chemical reaction) Oxygen capacity Oxygen content % hemoglobin saturation Oxygen delivery Oxygen consumption Oxygen content Oxygen capacity % hemoglobin saturation oxygen content = dissolved O 2 + oxyhemoglobin oxyhemoglobin = oxygen content - dissolved O %saturation of Hb = O 2 combine with Hb with O 2 O 2 capacity of Hb (or %SaO 2 ) X

31 ย Oxygen saturation %SaO 2 refer to the amount of oxygen being carried in the red blood cells size? Htc.? Pulse Oximeter.by utilizing selected wavelengths of light to noninvasively determine the saturation of deoxygenated and oxygenated hemoglobin 181 p Physiological shunt Physiological shunt (2-4% C.O.) 1. Bronchial artery: (lung parenchyma terminal bronchiole) PAO 2 O 2 sat. = 97.4% alveolar-arterial oxygen gradient pulmonary vein 2. Coronary vein: left atrium 2-4% CO bronchial artery coronary vein O 2 sat. = 97% PaO Thebesian vein left ventricle 184 Oxygen capacity of Hb In normal: Hb 15 gm/ 100ml. blood Hb 1 gm O ml (max.) Oxygen capacity = O 2 (max.) combine with Hb in 100ml. blood = 15 x 1.34 = 20.1 ml in 100ml. blood O ml ~ 20 vol% 15gm% 185 Oxygen content CaO 2 O 2 content = totalo 2 in blood (arterial blood) = dissolved O 2 + oxyhemoglobin 0.3 ml = (PO 2 x 0.003) + (O 2 capacity) x Hb x%sao mmhg = 1.34 x ml = 20.1 ml 19.8 ml A-V shunt 100% saturation ~ 20 ml 97% saturation 97% of (20.1 ml) = 19.5 ml 186

32 O 2 saturation of Hb %SaO 2 Oxygen content = dissolved O 2 + oxyhemoglobin oxyhemoglobin = Oxygen content - dissolved O 2 O 2 capacity of Hb %saturation of Hb = O 2 combine with Hb with O X O 2 capacity of Hb (or %SaO 2 ) 187 Oxygen content CvO 2 O 2 content = totalo 2 in blood (venous blood) = dissolved O 2 + oxyhemoglobin = (PO 2 x0.003) + (O 2 capacity) x Hb x %SvO 2 O 2 combine with Hb 40 mmhg = % saturation = % of (20.1 ml) = ml = ml = 15 ml 188 DO 2 Oxygen delivery O 2 content = total O 2 in blood (arterial blood) Venous blood PO 2 = 40 mmhg in 100ml. blood Arterial blood PO 2 = 100 mmhg ~ 20 ml (in 100 ml. blood) dissolved O 2 = ml = 0.12 ml dissolved O 2 = ml = 0.3 ml Q = 5 L/min cells Oxyhemoglobin = ml ~ 15 ml Oxyhemoglobin = 19.5 ml ~ 20 ml ~ 5 ml O 2 Q x (x10) (unit: L/min) or 250 ml/min 189 (if C.O. = 5000 ml/min) 190 DO 2 CaO 2 VO 2 Oxygen consumption in 100ml. blood oxygen content Arterial blood ~ 20 ml cells ~ 5 ml Venous blood ~ 15 ml 191 O 2 content in 100ml. blood Arterial blood ~ 20 ml cells ~ 5 ml Venous blood ~ 15 ml VO 2 Q = 5 L/min in 100ml. blood cells use ~ 5 ml C.O. = 5000 ml/min 5000 x 5 ml = 250 ml 100 Oxygen consumption 192

33 Oxyhemoglobin dissociation curve dissociation separation different PO 2 O 2 dissociation release O 2 from HbO 2 Hb + O 2 HbO 2 reversible reaction O 2 dissolved O 2 oxyhemoglobin %SaO 2 PO 2 O 2 capacity of Hb (~250 PO 2 100, 90, 80 mmhg 194 %SaO 2 Oxyhemoglobin dissociation curve Sigmoidal S shape curve Arterial blood Venous blood Oxyhemoglobin dissociation curve v a O 2 50% SaO 2 pressure %SaO 2 O 2 dissociation curve p.563 Oxyhemoglobin dissociation curve a Gas transportation in blood v unloading loading associated part or flat part oxyhemoglobin binding O 2 (chemical reaction) dissociated part or steep part dissolved O 2 PO 2 %SaO O 2 O 2 O 2 O 2 O 2 198

34 Factors affecting O 2 dissociation curve 1. PCO 2 2. H + concentration 3. temperature 4. 2,3 diaphsphoglyceric acid (2,3 DPG) in RBC ( β chain of oxyhemoglobin) Shift of O 2 dissociation curve shift to the left shift to the right curve shifts reflect altered affinity of Hb for O %SaO p.565 Factors O 2 affinity to Hb release O 2 Factors P50 Shift to left Shift to right O 2 affinity to Hb Normal o C, ph 7.4 PCO 2 40 mmhg Shift to right release O 2 PCO 2 ph Bohr effect 201 P50 O 2 affinity to Hb *** 202 Effect of 2,3 diaphosphoglyceric acid (2,3 DPG) 2,3 DPG RBC HbO 2 + 2,3 DPG Hb-2,3 DPG + O 2 2,3 DPG shift to right = HbO 2 release O 2 O 2 affinity to Hb 6 gm Hb/100 ml blood hypoxia (>2-3 hrs) 2,3 DPG anemia blood (in Blood bank) hypoxemia chronic lung diseases exercise p.566

35 a tasteless odorless gas that is a byproduct of combustion the early symptoms are quite nonspecific! anemia eg. motion sickness or heat exhaustion and include prolonged headache, nausea, dizziness, and vomiting Dissolved in plasma dissolved CO 2 (6%) 2. Diffuse to RBC dissolved CO 2 in intracellular fluid react with NH 2 -group carbaminohemogloblin react with H 2 O bicarbonate 207 Dissolved in plasma dissolved CO 2 (6%) Henry s law volume α partial pressure of that gas of dissolved gas solubility-20 times : CO 2 > O 2 in blood 100 ml: PCO 2 1 mmhg 20x(0.003) = 0.06 Dissolved CO ml 208 react with H 2 O bicarbonate in plasma slow in plasma (88%)*** in RBC *** (500 times faster) in RBC CA CO 2 + H 2 O H 2 CO 3 H + + HCO 3 Carbonic acid Bicarbonate CA: carbonic anhydrase 209 react with NH 2 - (amino group) carbaminohemogloblin in plasma in plasma in RBC CO 2 +R-NH 2 RNHCOOH RNHCOO + H + plasma protein carbamino compounds (6%) in RBC CO 2 + HbO 2 carbamino hemoglobin + O 2 protein part HbCO in Hb 2 210

36 Venous blood PCO 2 = 46 mmhg dissolved CO 2 = 46 x 0.06 ml = 2.7 ml Bicarbonate carbaminohb = 50.3 ml ~ 53 ml ~ 4 ml or ml/min (if C.O. = ml/min) average 210 ml/min in 100ml. blood CO 2 Arterial blood PCO 2 = 40 mmhg dissolved CO 2 = 40 x 0.06 ml = 2.4 ml Bicarbonate = 43.8 ml carbaminohb = 2.6 ml ~ 49 ml 211 VCO 2 Carbon dioxide production Carbondioxide content Arterial blood ~ 49 ml in 100ml. blood cells ~ 4 ml Venous blood ~ 53 ml 212 in 100ml. blood Carbondioxide content Arterial blood ~ 49 ml VCO 2 cells ~ 4 ml cells release in 100ml. blood C.O. = 5000 ml/min Venous blood ~ 53 ml ~ 4 ml 5000 x 4 ml 100 = 200 ml Carbondioxide production 213 tissue dissolved CO 2 CO 2 CO 2 +R-NH 2 RNHCOOH RNHCOO + H + *** RBC capillary CO 2 + H 2 O H 2 CO 3 H + + HCO 3 O 2 dissolved CO 2 (HbCO 2 ) CO 2 + HbO 2 carbaminohb + O 2 CO 2 pulm. capillary oxygenation p.568 H 2 O Cl - Chloride shift CO 2 + H 2 O H 2 CO 3 CA HHb= reduced Hb plasma Haldane effect HCO 3 + H + H + + HbO 2 *** buffered H + Hb - + O Peripheral blood 2 de-oxygenation plasma higher ph affinity to CO Haldane effect Carbon dioxide dissociation curve PO 2 carbaminohb: HbCO 2 release CO2 Oxygenation (@ lungs) ph HbCO 2 + O 2 HbO 2 + CO 2 53 vol% 49 vol% 4vol% affinity to CO 2 expired air arterial blood venous blood dissolved CO

37 more steep *** p

αo 2 : solubility coefficient of O 2

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