Gas Exchange

Ventilation

minute ventilation: V_E= V_Tx f V_T = tidal volume; f = breaths per minute

Dead Space: parts of the lung that are not perfused (trachea, bronchioles, unperfused alveoli)

normal dead space ~150 ml

normal tidal volume ~500 ml

does not contribute to gas exchange

alveolar ventilation - air that does reach perfused regions (alveoli)

Bohr equation:

anatomic dead space: conducting airways, etc.

alveolar dead space: overventilated relative to perfusion, or unperfused alveoli

Alveolar Ventilation: V_A = (V_T x f) - V_D = V_E = V_D

PaCO₂ equation:

k = 0.863

PaCO₂ is function of production and alveolar ventilation

Alveolar Gas Relationships

FIO₂is the same anywhere on earth (unless supplemental O₂, 0.21)

PIO₂ changes with barometric pressure, and thus altitude (P_B is normally 760 mm Hg; 747 in cleveland)

alveolar PO₂ is lower than atmospheric mostly due to PCO₂ in the alveoli

CO₂ ~ 4% of stale air

leads to Alveolar Gas Equation: PAO₂ = FIO₂(P_B-47) - 1.2(PaCO₂)

A-a gradient: A-aDO₂ = PAO₂(calculated) - PaO₂ (measure in blood gas)

normal is ~1-15 mm; greater than 20 on normal O₂ is usually abnormal
abnormal means there is an impairment of gas exchange

respiratory gas exchange ratio: R = VCO₂ / VO₂

usually 0.8 in healthy adults

A-a gradient increases with supplemental O₂

PO₂ in air ~150 mm; in alveous ~93 (see figure below)

air/alv drop mainly from PCO₂
shunt refers to normal V/Q imbalance, not physiologic shunt

A-a gradient of 100 is abnormal if on 100% oxygen

A-a gradient of 50 is normal if on Mt. Everest

Diffusion

follows Fick’s law

usually occurs rapidly (0.25 sec); blood is in contact with alveolus for ~0.75 sec so normally not problem

exercise has more effect on O₂ exchange

diffusion barrier really only show up with exercise (see figure below)

Oxygen Content – Arterial O₂ Content = dissolved O₂ + hemoglobin-bound O₂

dissolved O₂

dissolved O₂: Henry’s Law - dissolved is proportional to partial pressure over the liquid
dissolved O₂= 0.0031 x PaO₂
amount is small unless very high PaO₂

bound to hemoglobin

carrying capacity: 1.34 ml O₂ per gram of Hb
carrying capacity of blood = carrying capacity of Hb x Hb content of blood

usually given as ml O₂ / 100 ml blood

percent saturation = ( amount O₂ bound to Hb / O₂ carrying capacity of blood ) x 100
total amount bound to Hb: HbO₂ = 1.34 x Hb x saturation
PO₂ is only a measure of dissolved O₂; CaO₂ is content (HbO₂ + dissolved)

oxygen delivery

total oxygen content of blood = HbO₂ (1.34 x Hb x sat) + dissolved O₂ (0.0031xPO₂)
inadequate oxygen delivery causes:

reduced cardiac output
reduced Hb (anemia, bleeding, abnormal Hb)
reduced blood oxygen content

Oxyhemoglobin Dissociation Curve

shape and physiologic significance

can reconstruct curve from a few points:

PaO₂ mm	SaO₂ %
0	0
27	50 - P₅₀
40	75 - mixed venous point
60	90 - shoulder: inc PO₂ ¹ increase saturation
100	98 - normal saturation

curve is flat in physiologic range, so if increase PO₂ do not increase saturation much

shift to left with ß temp, ß PCO₂, Ý pH, ß DPG

Bohr shift due to:

(1) Ý PCO₂ and ß pH Þ shifts right, easy to unload O₂, occurs at tissue level

(2) ß PCO₂ and Ý pH Þ shifts left, easy to load O₂, occurs at alveolar level

carbon monoxide – does not affect measurement of PO₂

200 x affinity for Hb so displaces O₂
also increases affinity of remaining Hb for O₂
shifts curve to left
CaO₂ low, but PO₂ appears as normal

methemoglobin – shifts left: Fe²⁺ Þ Fe³⁺

Carbon Dioxide Transport

dissolved CO₂ obeys Henry’s law: is 20x more soluble than O₂

acconts for 10% of O₂ released to the alveolus

bicarbonate: from carbonic anhydrase reaction

90% of CO₂ stores
2/3 of bicarb is in plasma; 1/3 in RBC

carbamino compounds

CO₂ binds reversibly to Hb
deox Hb binds CO₂ more rapidly than oxy-Hb and CO₂-Hb facilitates O₂ release

Carbon Dioxide Dissociation Curve

nearly linear in physiologic range

means that increased vent in some areas can make up for poor exchange in others

Haldane Effect: deox blood holds more CO₂ at a given PCO₂ than ox blood

can bind more CO₂ with Hb when you give up O₂
better buffering of the H⁺ released to form HCO₃^-

Five Causes of hypoxemia – any level of PO₂ below normal range of 80-90 mm Hg

(1) Hypoventilation

PCO₂is inversely related to alveolar ventilation; normal vent/perf (V/Q) = 0.8 - 1.0

normal PAO₂ = 100; normal PACO₂ = 40

lower ventilation results in new steady state of increased PACO₂ and decreased PAO₂

no change in A-a gradient; leads to decreased PaO₂(arterial hypoxemia)

changes predicted by PACO₂ equation:

cannot diagnose hypoventilation if PCO₂ is not elevated

causes:

(1) drug intoxications
(2) CNS disorders
(3) NM disorders
(4) chest wall injuries
(5) COPD

treatment: increased FIO₂; but may progress to apnea, so intubation is better

summary: hypoventilation

(1) causes a decreased PAO₂ and PaO₂;
(2) causes an increased PACO₂ and PaCO₂
(3) is associated with a normal A-aDO₂ when it occurs acutely
(4) PAO₂ and PaO₂ increase with increased FIO₂

(2) Shunt – blood passes from right side of heart to left without contacting a ventilated alveolus

normally, 2-4% of blood bypasses the alveoli via bronchial circulation, etc.
pathologic shunt occurs when have an anatomic shunt

i.e. congenital heart disease, A-V malformations, pulmonary edema, pneumonia, pulmonary embolism

shunted blood mixes with oxygenated blood to lower the overall oxygen content
remember difference between CaO₂ and PaO₂: can only average CaO₂
PaCO₂ is usually normal or low from increased ventilation in normal alveoli
poor response to increased FIO₂ because of sigmoid dissociation curve; flat in physiologic range
measured clinically with A-a gradient on 100% oxygen

should kill effects of hypovent, V/Q imbalance, diffusion impairment

summary: shunt

(1) causes a fall in PaO₂
(2) is associated with a normal or decreased PaCO₂
(3) results in an increased A-aDO₂
(4) responds poorly to an increased FIO₂
(5) is measured clinically on 100% oxygen

(3) Ventilation-Perfusion Mismatch

most common cause of hypoxemia

some exists normally: V/Q = 3.0 in apices ; 0.6 in lower lung (normal V/Q = 0.8 to 1.0)

V/Q = infinity when no perfusion, zero when no ventilation (shunt)

summary: V/Q mismatch

(1) causes a decreased PaO₂ due to the low V/Q alveoli

(2) is usually associated with a normal PaCO₂

(3) is associated with an increased A-aDO₂

(4) characteristically responds well to even small increases in FIO₂

(5) is completely corrected by 100% oxygen

(6) high V/Q = ß PACO₂; low V/Q = hypoxemia

(4) Diffusion Impairment (rarely the sole cause of hypoxemia)

inversely prop to membrane thickness, directly to SA, diffusion constant, pressure gradient
diffusion impairment means it takes longer for cap PO₂ to come into equilibrium with alveolar
normally have 3x the needed contact time for adequate diffusion, but impairment could show up with exercise
role in hypoxemia is controversial; rarely the cause
summary: diffusion impairment

(1) causes a decreased PaO₂ but a normal PAO₂
(2) is associated with a normal PaCO₂
(3) causes an increased A-aDO₂
(4) responds well to an increased FIO₂

(5) Breathing a Low PIO₂ – high altitude or a low FIO₂ gas

Key Points: The Causes of Hypoxemia.

The four abnormal states associated with hypoxemia are: Hyporventilation, shunt, V/Q mismatch and diffusion impairment.
Of these, only shunt is not corrected by 100% oxygen.
Of these, V/Q mismatch responds best to small increases in FIO₂.