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Respiratory physiology II.

Learning objectives:

27. Pulmonary gas exchange.

28. Oxygen transport in the blood.

29. Carbon-dioxide transport in the blood.

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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.

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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 (Pgas)

depends on

� 1. the total pressure of the gas (Ptotal)

� 2. its fractional concentration (Fgas)

� Pgas= Ptotal • Fgas

� Partial pressures in physiology are often

referred to as „gas tensions” (mmHg).3

Calculation of partial pressures

in inspired air at sea level

� Ptotal = 760 mmHg (air consists of N2, O2, and H2O vapor)

� FN2= 0.78, FO2

= 0.21, FH20=0.01

� PN2= 760 • 0.78 = 593 mmHg

� PO2= 760 • 0.21 = 160 mmHg

� PH2O= 760 • 0.01 = 7 mmHg

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Calculation of partial pressures

on top of Mt. Everest

� Ptotal = 253 mmHg

� FN2= 0.78, FO2

= 0.21, FH20=0.01

� PN2= 253 • 0.78 = 197 mmHg

� PO2= 253 • 0.21 = 53 mmHg

� PH2O= 253 • 0.01 = 3 mmHg

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Calculation of partial pressures

on top of Mt. Everest, breathing O2

� Ptotal = 253 mmHg

� FN2= 0.0, FO2

= 1.0, FH20=0.0

� PN2= 253 • 0.0 = 0 mmHg

� PO2= 253 • 1.0 = 253 mmHg

� PH2O= 253 • 0.0 = 0 mmHg

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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 (Pgas)

� 2. the solubility of the gas (α)

� Henry-Dalton’s law:Cgas (ml/l)= α (ml/l x mmHg-1) • Pgas (mmHg)

� Importantly, net gas diffusion STOPS when the partial pressures are equilibrated (not when the concentrations are equal).

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To remember: Fick’s law of diffusion

C c

Diffusion surface (A)Membrane thickness (T)

diff.= ∆C •d • A

T

∆C=C-c

d= diffusion

coefficient

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Fick’s law application for gas transport

� V= gas transport rate (ml/min)

� ∆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)

V= ∆P •d • A

T

.V= ∆P • D.

diff.= ∆C •d • A

T

.

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diffusing capacity

Partial pressure values of respiratory gases in the alveoli,

arterial and mixed venous blood:

ESSENTIAL NORMAL VALUES!

Equilibration!

Equilibration!

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Determinants of PO2 and PCO2

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 (PH20=47 mmHg)

� 3. oxygen is being absorbed

� 4. carbon-dioxide is being added

� Alveolar PO2is INCREASED by ventilation, and

DECREASED by O2 uptake

� Alveolar PCO2is DECREASED by ventilation and

INCREASED by CO2 production

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Determinants of PO2 and PCO2 in the alveolar

air: alveolar ventilation

� If O2 and CO2

metabolism do not

change, increase of

alveolar ventilation will

increase or decrease

their partial pressures,

respectively

alveolar ventilation

breathing

at restalveolar

pO2

alveolar

pCO2

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Determinants of PO2in the alveolar air:

oxygen uptake

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( e.g. exercise)

Determinants of PCO2in the alveolar air:

carbon dioxide production

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( e.g. exercise)

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Determinants of PO2 and PCO2 in the alveolar air:

equations

� PACO2: alveolar partial pressure of

carbon dioxide

� VCO2: CO

2production (ml/min)

� Valveolar : alveolar ventilation (ml/min)

� PAO2: alveolar partial pressure of

oxygen

� VO2: O2 uptake (ml/min)

� Valveolar: alveolar ventilation (ml/min)

� PIO2:partial pressure of inspired

oxygen

PACO2= VCO2

/Valveolar •863 mmHg

. .PAO2

= PIO2– (VO2

/Valveolar •863 mmHg ). .

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863: conversion factor from STPD to BTPS condition

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?

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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.

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Not all alveoli are equal…

� The unique upright posture of the human body elicits regional

differences in alveolar ventilation and perfusion (four legged

animals will not have such problems).

� The apex has expanded alveoli, but EXCHANGE of air during

ventilation is low, the basis is well-ventilated.

� The apex is worst perfused, the basis is best perfused (see next

slide).

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alveolar pressure

dis

tan

ce f

rom

ba

seperfusion

Ventilation and perfusion zones in the lung

pressure in

pulmonary arterypressure in

pulmonary vein

No flow

Intermittent

flow

Continuous

flow

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Fortunately, in healthy people…

Bedrest puts every lung region in Zone III.

People with pulmonary infections MUST stay in bed!20

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However, …

� Ventilation/ perfusion (V/Q) ratio varies from the average 0.9-1.1 to

0.7 at base ---_ relatively underventilated,

2-3 at apex --- relatively underperfused

� This V/Q mismatch leads to a slight fall in PO2 (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 PO2 (right-left shunt, see next slide).

� In lung diseases (chronic inflammation, lung cancer) the amount of shunt

blood flow can increase greatly.

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The effect of V/Q mismatch and righ-left

shunt on arterial PO2

22Blood flow in the body

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2323

The Euler-Liljestrand mechanism

Local vasocontriction develops in hypoxic lung regions

High-altitude pulmonary edema (HAPE) (>2500 m)

vasoconstriction

lung oedema

Oxygen transport in blood:

dissolved + hemoglobin-bound

200 = 197 + 3 ml/l

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Dissolved oxygen

� Solubility in plasma (a) = 0.03 ml/l∙mmHg-1

� Negligible (<1%) under physiological conditions

� Medical physiology: hyperbaric oxygen treatment

(HBOT) at 2-2.5 ATA (inspired PO2= 1900 mmHg) can

mean 50 ml/l additional oxygen content!

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More details in the blood lecture…

hemoglobin

hemoglobin F

methemoglobin

carboxyhemoglobin26

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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!

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The Hb-oxygen binding/ dissociation curve

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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 AVDO2: 50 ml/l

� P50 (partial pressure O2 in 50% saturated blood):

26 mmHg

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Factors modulating Hb oxygen affinity,Bohr effect (pH related changes)

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Factors decreasing Hb oxygen affinity

� Carbon dioxide and acids (decreased pH) – the Bohr effect. This promotes

oxygen dissociation in the tissues with large CO2 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.

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Types of hypoxia – What is needed for

NORMAL oxygenation?

� Hypoxic hypoxia (arterial PO2is decreased): low inspired oxygen,

ventilation/diffusion/perfusion problems in the lung

� Anemic hypoxia (arterial PO2is normal), either Hb concentration is

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)

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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).

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CO2 transport in blood

� Bicarbonate

(chemically

dissolved) ~85%

� Carbamino groups

(Hb-bound) ~10%

� Dissolved as gas ~5%

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Hamburger shift

tissue

or

lung

red

blood cell

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CO2 transport in the blood

� The deoxygenated Hb can form more carbamino bonds and buffer more H+ ions, promoting uptake of CO2.

In the lungs, Hb oxygenation promotes the release of CO2. 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 CO2. The Cl--HCO3

-

exchange is facilitated diffusion.

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The Haldane effect

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Oxygen saturation CO2 binding

bound

bound

bound

bound

affin.

effect

effect

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Essential normal values

� CO2 in arterial blood:

480 ml/l

� CO2 in venous blood:

520 ml/l

� Arteriovenous CO2

difference (AVDCO2):

40 ml/L

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Caisson disease (decompression disease)

and divers disease

• N2 is not used in the body

• pressure changes -> solubility changes

• in great depth -> nitrogen narcose

• rapid ascent -> decompression disease

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normoventilation

hypoventilation

hyperventilation

eupnoe

bradypnoe

tachypnoe

orthopnoe

dyspnoe

asphyxia

What do these terms mean?

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