Respiratory physiology II.

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Garry Briggs
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1 Respiratory physiology II. Learning objectives: 29. Pulmonary gas exchange. 30. Oxygen transport in the blood. 31. Carbon-dioxide transport in the blood. 1 Pulmonary gas exchange The transport mechanism of respiratory gases across the alveolocapillary barrier is SIMPLE DIFFUSION. (Fick s law of diffusion). Diffusion takes place between a gas phase and a fluid phase, quantitative description of this diffusion requires the introduction of the following physical quantities: partial pressure of gases; solubility; and diffusing capacity. 2 1

Pulmonary gas exchange: partial pressure in gas mixtures In gas mixtures, the partial pressure is the pressure the gas would exert ALONE in the given space

$its fractional concentration (F gas ) P gas = P total F gas Partial pressures in physiology are often referred to as gas tensions (mmhg).$

2 Pulmonary gas exchange: partial pressure in gas mixtures In gas mixtures, the partial pressure is the pressure the gas would exert ALONE in the given space (volume). The partial pressure of a gas (P gas ) depends on 1. the total pressure of the gas (P total ) 2. its fractional concentration (F gas ) P gas = P total F gas Partial pressures in physiology are often referred to as gas tensions (mmhg). 3 Calculation of partial pressures in inspired air at sea level P total = 760 mmhg (air consists of N 2, O 2, and H 2 O vapor) F N2 = 0.78, F O2 = 0.21, F H2 0=0.01 P N2 = = 593 mmhg P O2 = = 160 mmhg P H 2O= = 7 mmhg 4 2

3 Calculation of partial pressures on top of Mt. Everest P total = 253 mmhg F N2 = 0.78, F O2 = 0.21, F H2 0=0.01 P N2 = = 197 mmhg P O2 = = 53 mmhg P H2 O= = 3 mmhg 5 Calculation of partial pressures on top of Mt. Everest, breathing O 2 P total = 253 mmhg F N 2 = 0.0, F O2 = 1.0, F H20=0.0 P N = = 0 mmhg 2 P O = = 253 mmhg 2 P H 2O= = 0 mmhg 6 3

Pulmonary gas exchange: partial pressure in fluids Gas molecules from the air (gas phase) are entering the blood (fluid phase) with simple diffusion, until a dynamic equilibrium (steady state) is

4 Pulmonary gas exchange: partial pressure in fluids Gas molecules from the air (gas phase) are entering the blood (fluid phase) with simple diffusion, until a dynamic equilibrium (steady state) is reached. At this point the partial pressure in the fluid is the same as that of the gas. At this steady state, the concentration of dissolved gas is determined by 1. the partial pressure of the gas (P gas ) 2. the solubility of the gas (α) Henry-Dalton s law: C gas (ml/l)= α (ml/l x mmhg -1 ) P gas (mmhg) Importantly, net gas diffusion STOPS when the partial pressures are equilibrated (not when the concentrations are equal). 7 To remember: Fick s law of diffusion C=C-c C c d= diffusion coefficient Membrane thickness (T) Diffusion surface (A) diff.= C d A T 8 4

5 Fick s law application for gas transport diff.= C d A T. V= gas transport rate (ml/min). V= P d A P= partial pressure difference (mmhg) determined by partial pressure differences in the alveolar air and in the blood D = diffusing capacity (ml/min mmhg -1 ) combining factors of gas quality, alveolocapillary barrier thickness, and barrier surface. D is NOT a constant! During exercise, for example, D increases (diffusion surface increases) T. V= P D diffusing capacity 9 Partial pressure values of respiratory gases in the alveoli, arterial and mixed venous blood: ESSENTIAL NORMAL VALUES! Equilibration! Equilibration! 10 5

Determinants of P O2 and P CO2 in the alveolar air The partial pressures of gases in alveolar air are different from the values of inspired air because: 1. the air is warmed to body temperature, 2.

6 Determinants of P O2 and P CO2 in the alveolar air The partial pressures of gases in alveolar air are different from the values of inspired air because: 1. the air is warmed to body temperature, 2. it becomes saturated with water vapor (P H 20=47 mmhg) 3. oxygen is being absorbed 4. carbon-dioxide is being added Alveolar P O2 is INCREASED by ventilation, and DECREASED by O 2 uptake Alveolar P CO2 is DECREASED by ventilation and INCREASED by CO 2 production 11 Determinants of P O2 and P CO2 in the alveolar air: alveolar ventilation breathing at rest alveolar po 2 alveolar pco 2 If O 2 and CO 2 metabolism do not change, increase of alveolar ventilation will increase or decrease their partial pressures, respectively alveolar ventilation 12 6

7 Determinants of P O in the alveolar air: 2 oxygen uptake ( e.g. exercise) 13 Determinants of P CO in the alveolar air: 2 carbon dioxide production ( e.g. exercise) 14 7

8 Determinants of P O2 and P CO2 in the alveolar air: equations.. P ACO2 = V CO2 /V alveolar 863 mmhg.. P AO2 = P IO2 (V O2 /V alveolar 863 mmhg ) P ACO2 : alveolar partial pressure of P AO2 : alveolar partial pressure of carbon dioxide oxygen V CO2 : CO 2 production (ml/min) V O2 : O 2 uptake (ml/min) V alveolar : alveolar ventilation (ml/min) V alveolar : alveolar ventilation (ml/min) P IO2 :partial pressure of inspired oxygen 863: conversion factor from STPD to BTPS condition 15 Perfusion limitation and/or diffusion limitation of gas transport The alveolar gas is being equilibrated with a MOVING fluid compartment (blood), therefore gas transport could be limited in theory by too little perfusion, or too slow diffusion (or combined) The blood spends ~ 0.75 second in the pulmonary capillary. Is this contact time enough for the equilibration of diffusing gases? 16 8

9 Capillary reserve time: almost 0.5 second! The gas equilibration takes place in 0.25 second, there is a large reserve at rest that can be used during exercise. In healthy lungs gas transport will ALWAYS be limited by blood flow (cardiovascular function). Medical physiology: lung diseases affecting diffusion will cause no symptoms at rest first, problems arise usually with exercise. 17 Not all alveoli are equal The unique upright posture of the human body elicits regional differences in alveolar ventilationand perfusion(four legged animals will not have such problems). The apex has expanded alveoli, but CHANGE in air during ventilation is small, the basis is well-ventilated. The apex is worst perfused, the basis is best perfused (see next slide). 18 9

Ventilation and perfusion zones in the lung pressure

pulmonary vein No flow Intermittent flow Continuous

healthy people Bedrest puts every lung region in Zone

10 Ventilation and perfusion zones in the lung pressure in pulmonary artery alveolar pressure pressure in pulmonary vein No flow Intermittent flow Continuous flow distance from base perfusion 19 Fortunately, in healthy people Bedrest puts every lung region in Zone III. People with pulmonary infections MUST stay in bed! 20 10

11 However, Ventilation/ perfusion (V/Q) ratio varies from the average to 0.7 at base ---_ relatively underventilated, 2-3 at apex --- relatively underperfused This V/Q mismatch leads to a slight fall in P O2 (and oxygen content) in the mixed blood in the pulmonary veins. In addition, venous blood from the bronchial veins and left heart are mixed in this blood further reducing arterial P O2 (right-leftshunt, see next slide). In lung diseases (chronic inflammation, lung cancer) the amount of shunt blood flow can increase greatly. 21 The effect of V/Q mismatch and righ-left shunt on arterial P O2 Blood flow in the body 22 11

12 The Euler-Liljestrand mechanism Local vasocontriction develops in hypoxic lung regions High-altitude pulmonary edema(hape) (>2500 m) vasoconstriction lung oedema 23 Oxygen transport in blood: dissolved + hemoglobin-bound 200 = ml/l 24 12

hyperbaric oxygen treatment (HBOT) at 2-2.

13 Dissolved oxygen Solubility in plasma (a) = 0.03 ml/l mmhg -1 Negligible (<1%) under physiological conditions Medical physiology: hyperbaric oxygen treatment (HBOT) at ATA (inspired PO 2 = 1900 mmhg) can mean 50 ml/l additional oxygen content! 25 More details in the blood lecture hemoglobin hemoglobin F methemoglobin carboxyhemoglobin 26 13

14 Hemoglobin-bound oxygen 1 tetrameric Hb molecule can bind up to 4 oxygen molecules. The binding sites interact with each other: binding an oxygen will increase oxygen binding (affinity) at the other sites. Saturatable binding, 1 g fully saturated hemoglobin carries 1.34 ml oxygen (Hüfner number). The AMOUNT of Hb-bound oxygen depends on the degree of saturation AND Hb concentration! 27 The Hb-oxygen binding/ dissociation curve 28 14

15 Essential normal values from the previous figure Hb oxygen saturation in arterial blood: 97-98%, in venous blood: 75%! Arterial oxygen concentration: 200 ml/l Venous oxygen concentration: 150 ml/l Arteriovenous oxygen difference AVDO 2 : 50 ml/l P 50 (partial pressure O 2 in 50% saturated blood): 26 mmhg 29 Factors modulating Hb oxygen affinity, Bohr effect (ph related changes) 30 15

16 Factors decreasing Hb oxygen affinity Carbon dioxide and acids (decreased ph) the Bohr effect. This promotes oxygen dissociation in the tissues with large CO 2 production and/or acidosis due to anaerobic metabolism. Elevated temperature: This promotes oxygen dissociation in tissues with high metabolic activity producing heat. 2,3 DPG produced in the red blood cells by glycolysis, maintains normal affinity. In conserved blood, low DPG levels can cause insufficient oxygenation in the transfused patient. HbF is not sensitive to DPG that helps to take up oxygen from maternal HbA. 31 Types of hypoxia What is needed for NORMAL oxygenation? Hypoxic hypoxia (arterial P O is decreased): low inspired oxygen, 2 ventilation/diffusion/perfusion problems in the lung Anemic hypoxia (arterial P O is normal), either Hb concentration is 2 decreased, or Hb ratio unable to carry oxygen too high (CO poisoning, methemoglobinemia) Ischemic (stagnation) hypoxia: blood flow is reduced in the tissues (cardiovascular cause) Histotoxic hypoxia: oxygen consumption is impaired (mitochondrial toxins such as cyanide) 32 16

Cyanosis usually indicates low saturation, but can be missing if Hb concentration is too low

17 Cyanosis a little orientation to clinical signs If the concentration of deoxygenated Hb is > 50 g/l, the mucosal membranes and the skin will get a bluish discoloration. Cyanosis usually indicates low saturation, but can be missing if Hb concentration is too low (anemia). 33 CO 2 transport in blood Bicarbonate (chemically dissolved) ~85% Carbamino groups (Hb-bound) ~10% Dissolved as gas ~5% 34 17

tissue or lung red blood cell Hamburger shift 35 CO 2 transport in the blood The deoxygenated Hb can form more carbamino bonds and buffer more H + ions, promoting uptake of CO 2.

18 tissue or lung red blood cell Hamburger shift 35 CO 2 transport in the blood The deoxygenated Hb can form more carbamino bonds and buffer more H + ions, promoting uptake of CO 2. In the lungs, Hb oxygenation promotes the release of CO 2. This is the Haldane effect. Another mechanism is the chloride shift (Hamburger shift), removing bicarbonate ions from the red blood cells, promoting the uptake of more CO 2.The Cl - -HCO 3 - exchange is facilitated diffusion

19 The Haldane effect Oxygen saturation CO 2 binding 37 bound bound affin. effect bound bound effect 38 19

(decompression disease) and divers disease N 2 is not used in the body pressure

20 Essential normal values CO 2 in arterial blood: 480 ml/l CO 2 in venous blood: 520 ml/l Arteriovenous CO 2 difference (AVDCO 2 ): 40 ml/l 39 Caisson disease (decompression disease) and divers disease N 2 is not used in the body pressure changes -> solubility changes in great depth -> nitrogen narcose rapid ascent -> decompression disease 40 20

21 What do these terms mean? normoventilation hypoventilation hyperventilation eupnoe bradypnoe tachypnoe orthopnoe dyspnoe asphyxia 41 21

Section Three Gas transport

Section Three Gas transport Lecture 6: Oxygen transport in blood. Carbon dioxide in blood. Objectives: i. To describe the carriage of O2 in blood. ii. iii. iv. To explain the oxyhemoglobin dissociation