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Scambi gassosi

Prof. Federico Lavorini


federico.lavorini@unifi.it
L’apparato respiratorio ha il compito di assicurare gli
scambi gassosi tra l’aria ed il nostro organismo.
In biologia il termine respirazione ha due significati
differenti:
Respirazione “polmonare”: scambi gassosi effettuati
dall’apparato respiratorio

Respirazione “cellulare”: produzione di energia all’interno dei


mitocondri delle cellule

I due fenomeni sono in effetti associati, perché i gas


respiratori scambiati dall’apparato respiratorio, e
veicolati dal sangue, vengono utilizzati e prodotti
proprio nella respirazione cellulare.
Nei vertebrati lo scambio dei gas avviene in tre fasi:

Polmone O2
1 Scambi gassosi
CO2
tra aria e sangue

Sistema circolatorio

2 Trasporto di
gas tramite il
sistema
circolatorio

Scambi gassosi Mitocondri


tra sangue
3
e tessuti O2
CO2
Capillari

Cellula
Nei polmoni gli scambi gassosi tra aria e sangue avvengono a
livello degli alveoli polmonari costituiti da un sottile strato di
cellule epiteliali.
La presenza nei polmoni delle numerosissime cavità alveolari
porta la superficie di scambio tra aria e sangue a circa 70 m 2

Sangue
ricco Sangue povero
di ossigeno di ossigeno

Bronchiolo

Alveoli
Capillari
sanguigni
Principles of Gas Exchange
• Gas movement between alveolar air and blood is a passive
process (pulmonary gas exchange) determined by the
concentration gradient for the particular gas.

• Normally, PaO2 is high and PaCO2 is low in alveolar air. The


opposite is true for the partial pressure of these gases in the
blood entering the lungs.

• It is these differences in partial pressures that produce


the driving force for oxygen to enter the blood and carbon
dioxide to leave the blood as blood flows through the
alveolar capillary bed.
Pulmonary and Tissue Gas Exchanges
Composizione e Pressione
parziale dei gas nell’aria
atmosferica

Percentuale Pressione parziale


O2 20.93 % 159 mm Hg
CO2 0.03 % 0.2 mm Hg
N2 79 % 600 mm Hg
Pressione parziale = percentuale x pressione totale della
miscela
Atmospheric Air vs. Alveolar Air
• H2O vapor 3.7 mmHg • H2O vapor 47 mmHg
• Oxygen 159 mmHg • Oxygen 104 mmHg
• Nitrogen 597 mmHg • Nitrogen 569 mmHg
• CO2 0.3 mmHg • CO2 40 mmHg
Transport of O2 and CO2

Pressure differences causes gas to diffuse


Alveolus Capillaries Tissues (fluid) Tissues (cells)

pO2 104 mmHg 95 mmHg 40 mmHg 5-40 mmHg

pCO2 40 mmHg 45 mmHg 45 mmHg 46 mmHg


Alveolar Gas Equation
PACO2
PAO2  PIO2 - F
PACO R2
PAO2  PIO2 - F
R Equation
Using the Alveolar Gas
40
PAO2  150 -
0.8
PAO2  100
Relationship between alveolar
ventilation and alveolar partial pressure
PO2 cascade in a hypothetical perfect lung

Perfect Lung
Effect of hypoventilation
Alveolar gas equation for hypoventilation

PACO2
PAO2  PIO2 - F
R
80
PAO2  150 -
0.8
PAO2  50
Diffusion of Gases
– Random molecular motion of
molecules with energy provided by
kinetic motion of the molecules
– All molecules are continually
undergoing motion except in
absolute zero temperature
– Net diffusion
• Product of diffusion from high to low
concentration
Gas Pressures
• Partial Pressure
– Pressure is directly proportional to the concentration
of gas molecules
– In respiration, there’s mixture of gases: O2, N2, CO2
– Rate of diffusion of each gas is directly proportional to
the pressure caused by each gas alone.
• AIR = total Pressure 760 mmHg
79% N2, 21% O2 = PPN2 = 600mmHg ,
PPO2 =160mmHg
Gas Pressure in Fluid
• Determined by its concentration and by
solubility coefficient

• HENRY’s LAW : Pressure = concentration


solubility coefficient
Solubility of Gases in
body temp.
• O2 = 0.024
• CO2 = 0.57 - 20x more soluble than O2
• CO = 0.018
• N2 = 0.012
• He = 0.008
Respiratory membrane
Capillary Base Membrane
Interocclusal
Alveolar Epithelial Base Membrane Capillary Epithelial Cells
Clearance
Alveolar Epithelial Cells

Liquid Layer Containing RBC


Alveolar Surfactant

Normally, area of RBC


respiratory Alveoli Capillary

membrane is very
large being beneficial
to gas exchange
RBC
Thickness of
respiratory
membrane is
close related to
diseases Structural Diagram of Respiratory
membrane
Legge di Fick
Descrive la diffusione di un gas
attraverso i tessuti:

Vgas = A/T x ΔP x D

A: superficie tissutale;
D: costante di diffusione del gas
ΔP (P1-P2): differenza di pressione
parziale del gas tra i due lati.
T: spessore del tessuto.

A, D and T are replaced by a single constant DL= Vgas/P1-P2


When CO is the gas being used measured P2 is ignored, then
DLCO= VCO/PACO
Factors that affect Rate of Gas Diffusion
through Respiratory Membrane
1. Thickness of membrane
• Increased (e.g. edema, fibrosis)
2. Surface area of membrane
• Decreased ( e.g. emphysema)
3. Diffusion coefficient of Gas in substance of
membrane
• Gas’ solubility
4. Pressure difference
• Difference between partial pressure of gas in alveoli and
pressure of gas in pulmonary capillary blood
Gas diffusion pathway
Alveolar-capillary
membrane
Red cell
Alveolus

O2 O2+ Hb HbO2
CO CO+Hb HbCO

ΔP
(driving pressure)

Carbon monoxide is used as a surrogate for O2


Alveolar-capillary
membrane
Red cell
Alveolus

O2 O2+ Hb HbO2
CO CO+Hb HbCO

ΔP
(driving pressure)
DL: overall diffusion capacity;
DM: diffusion from alveolar gas up to the red cell (“membrane
component”);
Θ . VC: diffusion for the red cell membrane to Hb molecules (“red cell
component”);
Why CO is preferred over O2 ?

 Not normally present in alveoli/blood


Binding affinity ̴ 200 times greater than that of
O2
 Transfer is entirely diffusion limited

O2 is perfusion limited in normoxic conditions


Single breath technique (DLCOsb)

1. Respiro tranquillo
2. Espirazione non forzata fino a RV, per
non più di 6 sec
3. Rapida (<4 sec) inspirazione a TLC
(volume inspirato >85% VC)
4. Tempo di apnea di 10 ± 2 sec (evitare
manovre di Valsalva o Mueller)
5. Espirazione in < 4 sec

il soggetto inala una miscela composta


da CO 0.3% + gas inerte normalmente
assente (elio 10-14%)+ ossigeno (18-
21%) e azoto, in percentuali variabili in
base alla miscela standard utilizzata

Macintyre N et al. Standardisation of the single-breath determination of carbon


monoxide uptake in the lung. Eur Respir J 2005; 26: 720-735.
Indications
 Evaluation and f/u of parenchymal lung diseases including IPF;
diseases associated with dusts (asbestos, silicosis); sarcoidosis;
pulmonary involvement in systemic diseases (rheumatoid
arthritis, lupus, Wegener’s).
 Evaluation of the effects of chemotherapy agents or other drugs.
 Evaluation and f/u of emphysema and differentiating among
COPD phenotypes
 Evaluation of PV diseases (eg, PPH, PE, or pulmonary edema)
Increased DLCO
 Increased blood flow: exercise, left to right shunt,
hyperdynamic state.
 Increased Hb
 Increased pulmonary capillary blood volume
 Obesity (secondary to increased blood volume?)
 Asthma (increased DM? or increased blood volume?)
 Intrapulmonary hemorrhage.
Isolated low DLCO

 Pulmonary vascular abnormalities (e.g.


embolism, vasculitis, hypertension)
 Interstitial lung disease (early disease ->
low DL,CO with normal lung volumes)
 Anemia: 50% reduced Hb -> 40% reduced
DLCO
 Early emphysema
Low DLCO with other abnormalities
 Restrictive pattern: interstitial lung disease.

 Obstructive pattern: reduced DLCO, particularly


in moderate to severe obstruction combined
with increased lung volumes (hyperinflation)
suggests emphysema.
Ventilation-Perfusion Ratio
• A concept developed to help us understand
respiratory exchange where there is
imbalance between alveolar ventilation
(Va) and alveolar blood flow (Q)

• Areas in lung with well ventilation but no


blood flow or excellent blood flow but no
ventilation
Ventilation-Perfusion Ratio
Va/Q = normal
• If Va is 0 (zero), but with perfusion: Va/Q
=0
• If Va is present, but no perfusion Va/Q =
infinity
• In both: there is no gas exchange
Blood flow and ventilation are
uneven within the lungs
Ventilation or Perfusion

Perfusion ( Q )
L/min

Ventilation
( VA )
0
Apex of Lung Base of Lung
Because of the effect of gravity, lung perfusion (Q), and
ventilation (VA) increase from the top (apex) to the
bottom (base) of the lung.
Effect of hydrostatic P on
regional pulmonary blood flow
• From apex to base capillary P  (gravity)
– Zone 1: no flow
• alveolar P > capillary P
• normally does not exist
– Zone 2: intermittent flow (toward the apex)
• during systole; capillary P > alveolar P
• during diastole; alveolar P > capillary P
– Zone 3: continuous flow (toward the base)
• capillary P > alveolar P
– During exercise entire lung  zone 3
Balancing ventilation and perfusion
• Regional differences in ventilation and blood flow cause the top
of the lung to be overventilated and the bottom of the lung
to be overperfused under normal conditions.

• Regional differences in the ratio of ventilation to perfusion result


in regional differences in gas exchange from the top to the
bottom of the normal lung.

• Because of ventilation-perfusion imbalance, blood leaving the top


of the lung has a higher PaO2 and a lower PaCO2 than blood
leaving the base of the lung.
Normal ventilation-perfusion
imbalance
VA / Q mismatch from top to
bottom of the lung

Ventilation/perfusion ratio decreases down the lung


Ventilation-Perfusion ratios
• Normally alveolar ventilation is matched to pulmonary
capillary perfusion at a rate of 4L/min of air to
5L/min of blood
• 4/5 = 0.8 is the normal V/P ratio

• If the ratio decreases, it is usually due to a problem


with decreased ventilation

• If the ration increases, it is usually due to a problem


with decreased perfusion of lungs
Ventilation Perfusion Ratios
PO2 = 150
PCO2 = 0

PO2 = 40 PO2 = 100 PO2 = 150


PCO2 = 45 PCO2 = 40 PCO2 = 0
No flow

CO2 = 45 . . .
Low VA/Q Normal VA/Q High VA/Q

Increase in Increase of
physiologic shunt physiologic dead
blood: blood that is space: area where
not oxygenated as it oxygenation is not
passes the lung taking place
PO2 = 40
PCO2 = 45
PO2 = 100
50 PCO2 = 40
.
Low VA/Q
Base
PCO2 (mm Hg)

.
Normal VA/Q
PO2 = 150
PCO2 = 0

Apex

.
High VA/Q
50 100 150
PO2 (mm Hg)