Respiration Part 2, Lectures 8 to 14, Jan 2011

7/27/2019 Respiration Part 2, Lectures 8 to 14, Jan 2011

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What the USMLE expects you to be able to do1. Describe and contrast the terms total (minute) ventilation, dead

space ventilation and alveolar ventilation.

2. Describe, using quantitative terms, minimum (BMR) and maximum

oxygen uptake.

3. Define the respiratory quotient (RQ) and respiratory exchange ratio

(R); list values for metabolism of fat, carbohydrate, protein.

4. Calculate alveolar PO2 from inspired PO2 and inspired O2 fraction

(% O).

5. Calculate alveolar ventilation from CO2 output and PaCO2.6. Calculate arterial (= alveolar) PCO2 from alveolar ventilation and

CO2 production.

7. Diagnose hyperventilation and hypoventilation using arterial blood

gases.

VI. Ventilation (Alveolar-, Dead Space and Total Ventilation)


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75400

PCO2 (mmHg)

Pathway of O2 from airway opening to tissue

PO2 (mmHg)

1500 75

O2-Partial pressureinspiratory

alveolar

arterial

mixed-venous

mitochondria

Lung ventilation

Circulation

Tissue metabolism

Diffusion

Cardiacoutput

Perfusion

metabolism

Ventilation

O2CO2

CO2O2 CO2

O2Lung

Perfusion

Diffusion


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B. After inspiration

Fresh

air

Inreases by VT

Mixing

Total-, Alveolar and Dead Space Ventilation

Fresh air

inspired

VT

VT VD= VA

VT = VD + (VT- VD)

VT FR = VD FR + (VT-VD) FR

VE = VD + VA

VA = VE - VD

A. Before inspiration

Alveolus

Deadspac

e

Alveolar

gas

VDUsed

alveolar

air

B. After inspiration, just

before expiration

Freshair

Inreases by VT

VT VD= VA


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VDVT - VD

VT

C. After expiration

Alveolar

gas

Alveolus

FA FI

FA

Mixing

Mixed expiratory

VT

FE

Usedalveolarair

B. After inspiration, justbefore expiration

Freshair

Inreases by VT

VT

VD= VA

Calculation of dead space using the Bohr equation


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(VT VD) FA + VD FI

VT FE

VD

VT=

O2

FE - FA

FI - FA=

VDVT - VD

VT

C. After expiration

Alveolar

gas

Alveolus

FA FI

FA

Mixing

Mixed expiratory

VT

FE

Calculation of dead space using the Bohr equation

CO2

FA - FE

FA

Eq. 3

VD

VT=

O2

PE - PA

PI - PA=

CO2

PA - PE

PA

Eq 4


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Metabolic Rate:the demand for oxygen Uptake

BMR = basal metabolic rate = VO2

250 ml per minute at 37 C (98.6 F)

275 ml per minute at 38 C (100.6 F)

225 ml/min at 36 C (96.6 F)


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Maximum O2 Uptake

The watt is the SI standard unit of

power (energy per unit time, joules/sec).

0 100 200 300

Work rate (watts)

0

2

4

6.5

VO2 max

VO2(

l/min)


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Respiratory Exchange Ratio (R)

Definition: R = CO2 output/O2 uptake

For carbohydrates (glucose):

C6H12O6 + 6O2 6CO2 + 6H2O

R =6CO2

6O2= 1

For fats, R = 0.7; proteins, R = 0.8


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Partial pressure of gases in a gas mixture

PtotalGas-mixture

P1

Dalton's law: Ptotal= P1+ P2+ P3

(Temperature and Volume constant)

P2P2


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Partial pressure of Gases in a Gas-mixture

Ideal Gas law :

Px V = Mx R T ..... applied for component x

(PB- PH2O) V = M R T ..... applied for the Sum of dry gases

Division

Px = Fx ( PB- PH2O )

PB = P1 + P2+ ..... + Pn+ PH2O

Total pressure(Barometric pressure) Partial pressure ofComponent 2

(for example O2 )

Partial pressureOf H2O

Px

PB-PH2O

Mx

M= Fx=

Fraction of x


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IV. Clinical CalculationsUsed inPulmonary Medicine

O2

A. Inspired PO2:PIO2 = FIO2 x (PB PH2O)

PIO2 = .21 x (74747) = 147mm Hg

At sea level:

PIO2 = .21 x (347 47) = 63 mm Hg

At 20,000 feet:

At 29,035 feet:PIO2 = .21 x (247 47) = 42 mm Hg


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PIO2

PAO2 = PIO2

Alveolar PO2 (PAO2)

O2

CO2

PEO2

PaO2PvO2

PACO2 = 0If no pulmonarygas exchange:


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CO2

PAO2 = PIO2PACO2

R

PIO2 PEO2

Alveolar PO2 (PAO2)

PaO2PvO2

O2


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PAO2 = PIO2 PACO2

If R < 1:

Examples

PAO2 = 147 40 = 107 mm Hg

If R = 1:

O2

PAO2 = PIO2 R

PACO2

PAO2= 147 = 97 mm Hg0.840


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AlveolarPCO2 (PAO2)

PACO2 =VCO2

VA

X 863

VA

VCO2

In tissue produced VCO2


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Example:

VCO2(normal) = 225 ml/min

VA(reduced) = 2250 ml/min

PACO2 = 225/2250 x 863 = 86.3 mm Hg

Patient with normal metabolicrate and depressed brain stem

What is the patients alveolar PCO2?


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Alveolar Ventilation

PACO2 = x 863VA

VCO2

VCO2

PACO2

x 863VA =

225

86.3x 863From example: VA = = 2250 ml/min


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O2

CO2

Alveolar ventilation and alveolar gas partial pressures

Quiet ventilation

A

A

PAO2

PACO2

D

D

PICO2

PIO2160

120

80

40

05 10 15

Alveolar ventilation, VA(lmin-1)

Alveo

larpart

ialpres

sure,

PA

(mm

H

g)


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Definition of alveolar ventilation

Normoventilation: Normal alveolar ventilatione.g. PaCO2normal (= 40 mmHg)

Hyperventilation: Alveolar ventilation is increased in excess ofmetabolic needs, therefore:

PaCO2 is reduced below normal (< 40 mmHg)

Hypoventilation: Opposite of hyperventilatione.g. PaCO2 is above normal (> 40 mmHg)


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KEY CONCEPTS1. Alveolar ventilation is the volume of fresh (nondead

space) gas entering the respiratory zone per minute. It

can be determined from the alveolar ventilation equation,that is, the CO2 output divided by the fractional

concentration of CO2 in the expired gas.

2. The concentration of CO2 (and therefore its partial

pressure) in alveolar gas and arterial blood is inverselyrelated to the alveolar ventilation.

3. The anatomic dead space is the volume of the

conducting airways.

4. The physiologic dead space is the volume of lung that

does not eliminate CO2. It is measured by Bohr's methodusing arterial and expired CO2.

5. The two dead spaces are almost the same in normal

subjects, but the physiologic dead space is increased in

many lung diseases.


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VII. Pulmonary Gas Exchange

What the USMLE expects you to be able to do

1. Name the factors that affect diffusive transport of a gas between alveolargas and pulmonary capillary blood (Ficks Law).

2. Describe the kinetics of oxygen transfer from alveolus to capillary and the

concept of capillary reserve time (i.e., the portion of the erythrocyte

transit time in which no further diffusion of oxygen occurs).

3. Calculate diffusing capacity from carbon monoxide uptake and carbon

monoxide partial pressure.

4. Contrast the uptake of O2, CO, and N2O from the lungs to pulmonarycapillary blood.

5. Describe why normal subjects at high altitude or patients with lung

disease may have a diffusion limitation during exercise.


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Alveolar membrane

Erythrocyte

Alveolo-capillary membrane


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Diffusion law

Area, A Thickness, TP1

P2

Diffusion rate, V

~ ~DLCO2~ 20 DLO2 , because aCO2~ 20 aO2Diffusion problems may occur for O2 ,

but not for CO2 !

DL = d a

SolubilityDiffusioncoefficient

Diffusioncapacity

Vgas = DL (P1-P2)

A

T


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Diffusing capacity is measured using

carbon monoxide gas

DL=V

gas

P

PaCO = 0

DLCO=V

CO

PACO - PaCO

DLCO =2 mmHg

= 25 ml/min/mmHg50 ml/min


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Normal Factors That Influence

Diffusing Capacity

Exercise. Diffusing capacityincreases = recruitment anddistension of pulmonary capillaries &better matching of blood flow and

ventilation. Body Position. Supine = increased

pulmonary capillary volume and moreeven distribution of pulmonary bloodflow.

Body Size. = Lung size = surfacearea.


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Pathological Factors That reducesDiffusing Capacity

Pathology of air-blood barrier ( thickness or surface area)

capillary volume hemoglobin.Examples: COPD, anemia, fibrosis, pulmonary

edema, pneumonia.


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0 100%Contact distance

120

80

40

0

PO

(mmHg)2

alveolar(PA)

or transit time

O2 uptake from alveolar gas into lung capillary blood

PAO2

Alveolar

capillarymembrane

Pc'O2PvO2

End-

capillary

(Pc')Capillary

Mixedvenous

(Pv)

Driving

Pressure difference


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Diffusion limitationAnd alveolar-end capillary O2 Partial pressure difference

1. Advantage for CO2:PCO2 equality between gas and blood

does exist, even if there is no equality

for O2 (e.g. interstitial edema with low DO2),Thus, in each alveolus Pc'CO2= PACO2

PAO2

(Pv)

(Pc)

alveolar(PA)

Alveolar

capillary

membrane

Pc'O2PvO2

PO2

ACDO

> 02

(Pv)(Pc)

alveolar(PA)

0 100%Contact distance

PCO2CADCO = 02


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Effect of low alveolar PO2

Normal DL

Low DL

Diffusion

limitation

0 0.25 0.50 0.75

Time in capillary (sec)

PO

2(mm

Hg

)

0

50

25

Alveolar

exercise rest


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Perfusion limitation

Alveolar

0 0.25 0.50 0.75

Transit time (sec)

PO2

(mmH

g)

0

100

exercise

40

rest

perfusion limitation

PA = PC = No more transfer


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Alveolar

00 0.25 0.50 0.75


PartialPressur

e

N2O

Start of capillary End of capillary

perfusion limitation

PA = PC = No more transfer

Nitrous oxide transfer is perfusion

limited


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Alveolar

00 0.25 0.50 0.75


PartialPress

ure


CO

Diffusion limitation

PA > PC when blood

leaves capillary.

No more transfer

Carbon monoxide transfer is

diffusion limited


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Diffusion limitation vs. perfusion

limitation of gas transfer

O2 (normal)

O2 (abnormal)

Alveolar

0

0 0.25 0.50 0.75

Time in capillary, sec

P

artialPressure


CO

Diffusion

limitation

N2O

Perfusion limitation


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KEY CONCEPTS

1. Fick's law states that the rate of diffusion of a gas

through a tissue sheet is proportional to the area of

the sheet and the partial pressure difference across it,and inversely proportional to the thickness of the

sheet.

2. Examples of diffusion- and perfusion-limited gases

are carbon monoxide and nitrous oxide, respectively.

Oxygen transfer is normally perfusion limited, but

some diffusion limitation may occur under some

conditions, including intense exercise, thickening of

the blood-gas barrier, and alveolar hypoxia.

3. The diffusing capacity of the lung is measured usinginhaled carbon monoxide. The value increases

markedly on exercise.

4. Carbon dioxide transfer into the blood is probably not

diffusion limited.


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VIII. Pulmonary Circulation

What the USMLE expects you to be able to do

1. Contrast the systemic and pulmonary circulations with respect to

pressures, resistance to blood flow, and vascular response to hypoxia.

2. Describe the normal anatomical shunts that cause reduced arterial PO2.

3. Describe how pulmonary vascular resistance changes with

alterations in cardiac output or pulmonary arterial pressure, lung

volume, and alveolar hypoxia.

4. Describe the potential causes of pulmonary edema and pleural

effusion.

5. Describe the causes of ventilation perfusion mismatch in normal

lungs and the compensatory mechanisms to correct V/Q mismatch.

Intravascular pressures in Lung- and systemic circulation


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Intravascular pressures in Lung and systemic circulation

Pressure drop

Lung

Vein

20/10 (mmHg)

7,5 6,8

Pu

lmonarycircu

lation

Rightatrium

Leftatrium

Sys

tem

icc

irc

ulation

Pressure drop

Vein

Tissue

Heart

(mmHg) 120/82

20

4

ArteryAverage pressure: 14 ArteryAverage pressure: 100

Rightventricle

Leftventricle


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Control of Pulmonary Vascular Resistance

(PVR)

Cardiac output

Mechanisms


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RA RVPA PAOP

wedge

pressure

Left Atrial Pressure is Measured via a Pulmonary Artery


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Dependence of pulmonary vascular resistance on lung volume

High Lung volumeLow Lung volume

Recoil force

Alveolus

alveolarcapillary

Alveolar septum

Residu

alvolume

FRC

TLC

Pulmonaryvas

cular

resistance

Lung volume0

Total

Extra alveolar

alveolar


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(PVR)

Good

matches

V and Q

DecreasesShunt effect

Good for fetus

Bad after birthCauses

pulmonary

hypertension

Opposite to systemic circulationwhere hypoxia vasodilation (see

Notes page)

Mechanism: hypoxia inhibits Kv

Channels, depolarizes, open Ca++

Channels, muscle contracts.

2 agonists

dilate

Hypoxia

High altitude, hypoVAHAPE


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(PVR)

Good

matches

V and Q

DecreasesShunt effect

Good for fetus

Bad after birthCauses

pulmonary

hypertension

Opposite to systemic circulationwhere hypoxia vasodilation (see

Notes page)

Mechanism: hypoxia inhibits Kv

Channels, depolarizes, open Ca++

Channels, muscle contracts.

2 agonists

dilate

Hypoxia

High altitude, hypoVAHAPE


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Pressure inAlveolar space (PA)

Pressure in pulmonaryvein (Ppv)

Pressure in pulmonaryartery (Ppa)

Perfusion

Hight

Zone

III

Zone

II

Zone

I

Distribution of perfusion in the lung

in an upright position

PA > Ppa > Ppv

Ppa > Ppv > PA

Ppa > PA > Ppv


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O2

Thebesian

veins

Bronchial veins

PA

PV

AO

NormalAnatomical Shunts

Anatomical Shunts Lower Arterial PO2


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O2

PA

PV

AO

PulmonaryAV fistula

VSD

Abnormal anatomical shunts

4 examples

PFO

PDA


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KEY CONCEPTS


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KEY CONCEPTS1. The pressures within the pulmonary circulation are much lower

than in the systemic circulation. Also the capillaries are exposed to

alveolar pressure, whereas the pressures around the extra-alveolar

vessels are lower.2. Pulmonary vascular resistance is low and falls even more when

cardiac output increases because of recruitment and distension of

the capillaries. Pulmonary vascular resistance increases at very

low or high lung volumes.

3. Blood flow is unevenly distributed in the upright lung. There is amuch higher flow at the base than the apex as a result of gravity. If

capillary pressure is less than alveolar pressure at the top of the

lung, the capillaries collapse and there is no blood flow (zone 1).

4. Hypoxic pulmonary vasoconstriction reduces the blood flow to

poorly ventilated regions of the lung. Release of this mechanism is

responsible for a large increase in blood flow to the lung at birth.

5. Fluid movement across the capillary endothelium is governed by

the Starling equilibrium.

6. The pulmonary circulation has many metabolic functions, notably

the conversion of angiotensin I to angiotensin II by angiotensin-

converting enzyme.


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IX. Gas Transport by the BloodWhat the USMLE expects you to be able to do

1. Describe which forms O2 is transported in the blood and beable to analyze the O2 dissociations curve.

2. Identify, using an oxygen dissociation curve, the normal values

of saturation, content, and partial pressure of arterial and mixed

venous blood.

3. Identify the factors affecting the O2 dissociation curve and

describe their effects

3. Compare the effects of carbon monoxide exposure versus anemia

on O2 transport.

4. Describe and contrast the processes of oxygenation and oxidation of

hemoglobin

4. Describe the forms of CO2 transport from tissues to lungs and therelative importance of each form.

5. Define the Bohr- and Haldane effects and describe their impact on

O2 and CO2 exchange in the lungs and tissues


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CO2 = a O2 PO2 HENRY`s law

Solubility coefficient

0 75 150 225 300 375 450

O2 Partial pressure, PO2 (mmHg)

200

150

100

50

0O2Concen

tra

tion

,CO

2(ml

STPD

l-1

)

Physically dissolved oxygen

O Binding curve of the blood


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O2 Binding curve of the blood

ch

emicallyboun

d(HbO

2)

O2-C

apa

ty=

Maxi

ma

lc

hem

ical

ly

bou

ndoxygen

phys

ica

lly

diss

olve

d(aO

2

PO

2)

O2

Conc

en

tra

tion

inb

loo

d,

CO

2

(ml

STPD

/l)

200

150

100

50

0

0 15075 225 300 375


E ilib i b t h i ll di l d


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PO2= PO2

Gas

A B

O2 physicallydissolved

O2

Equilibrium between physically dissolvedand chemically bound gas

PO2= PO2

BA

Newequilibrium

PO2 > PO2

A B

AddingHemoglobin

Hb


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O2 Binding curve of hemoglobin

Hemoglobin

0.50

P0.5 = 27 mmHgO

2Sa

tura

tion,

SO

2

1.0

0.8

0.6

0.4

0.2

00 40 80 120


40 mmHg

0.75

100 mmHg

0.98


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O2 Binding curve of hemoglobin

1.0

0.8

0.6

0.4

0.2

0

O2

Sa

tur

ation,

SO

2

0 40 80 120


P0.5 = 27 mmHg

0.50

O2 Binding curve of the blood

chem

ica

lly

boun

de

d(HbO

2)

200

150

100

50

0

O2

Concen

tra

tion

inbloo

d,

CO2

(mlS

TPD

/l)

1500 75 225 300 375


phys

ica

lly

diss

olve

d(aO2

PO

2)

I fl O


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Influences on O2 binding curve of the blood

Decreases in affinity = Right shift

Increases in affinity

= Left shift

O2 Partial pressure, PO2(mmHg)

1,0

0,5

00 40 80 120

O2

Saturatio

n,

SO2


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100

80

60

40

20

0

0 20 40 80 10060

PO2

(mmHg)

Hemoglobinsaturation(%)

40 mmHg 7.4

26 mmHg 7.6

61 mmHg 7.2

pH

Effects of pH and CO2

PCO2

100

80

60

40

20

0

0 20 40 80 10060

PO2

(mmHg)

40 mmHg 7.4

40 mmHg 7.6

40 mmHg 7.2

pH

Effect of pH

PCO2

H++

Hemoglobin

O2+

H+

100

80

60

40

20

0

0 20 40 80 10060

PO2

(mmHg)

61 mmHg 7.4

40 mmHg 7.4

26 mmHg 7.4

PCO2 pH

Effect of CO2

+ +

H2N NH2

NH-COO-

Carbamino hemoglobin

O2CO2

H2N H2N

H2N

NH2

NH2

BOHR Eff t H+ i d O bi di


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BOHR - Effect : H+ impedes O2 binding

Heme

H

+

O2

H+

Heme

O2

H+ + HCO3- CO2+ H2O

Effect of temperature


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Effect of temperature

100

80

60

40

20

0

Hemoglobin

saturation(%)

0 20 40 60 80 100

PO2

(mmHg)

3733

41


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Effect of DPG: + DPG O2+a a a ab b b b

4

Hemoglobin

saturation

( % )

100

80

60

40

20

0

0 20 40 80 10060

(mmHg)

PO2

[DPG]

2 mM

4 mM

6 mM

I fl bl d O bi di


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Influences on blood O2binding curve

Decreases in affinity = Right shift

Increases in affinity

= Left shift

O2 Partial pressure, PO2(mmHg)

1.0

0.5

00 40 80 120

O2

Saturatio

n,

SO2

H+ concentrationBohr-Effect

CO2 concentration

Temperature

2,3-BPG concentration

C b h l bi (HbCO)


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normal blood

(0 % HbCO)

0 40 80 120

O2partial pressure, PO

2(mmHg)

200

150

100

50

0

O2concentra

tion(ml/l)

Carboxyhemoglobin (HbCO)

Half of O2 capacity

(50 % Anemia, 0 % HbCO)

50 % CO bounded

(50 % HbCO)


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3 Forms of CO2 in the blood

CO2 + H2O HCO3- + H+1. CO2 2. Bicarbonate

CO2 + R-NH2R-NH- COO- + H+3. Carbamate

Reactions from CO entry into the blood from the tissue


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Tissueor

Lung

ErythrocytePlasma

Reactions from CO2 entry into the blood from the tissue,

and from CO2 release from the blood in the lung

CO2 CO2 CO2+Hb

O2

-OOC-Hb

Pr-

HPr

+

Carbo-

anhydrase

H+

Hb-

O2

+

+

HHb(Haldane-

Effect)

Cl- Cl-

H2O+

HCO3- +H+HCO3

-

+

H+

H2O+

CO2 dissociation curve


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43 ml/l

5 mm Hg

0 20 40 60 80 100

CO2 Partial pressure (mm Hg)

600

400

200

0

CO

2Concen

tration(ml/l)

2

arterial

mixed

venous

dissolved


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Acidification causes CO2 release from binding site

H+ CO2

H++ HCO3- H2O + CO2

adding released

CCO2

PCO2

+ H+


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Globin

Heme

O2

H+ + HCO3-

CO2 + H2O

H+ binding

A: Bohr effect

O2 affinity

Heme

H+ + HCO3- CO2 + H2O

O2

B: Haldane effect

O2 binding

H+ binding

CO2 binding


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KEY CONCEPTS

1. Most of the O2 transported in the blood is bound to

hemoglobin. The maximum amount that can be bound is called

the O2 capacity. The O2 saturation is the amount combined withhemoglobin divided by the capacity and is equal to the

proportion of the binding sites that are occupied by O2.

2. The O2 dissociation curve is shifted to the right (that is, the O2

affinity of the hemoglobin is reduced) by increases in PCO2, H+,

temperature, and 2,3-diphosphoglycerate.3. Most of the CO2 in the blood is in the form of bicarbonate, with

smaller amounts as dissolved and carbamino compounds.

4. The CO2 dissociation curve is much steeper and more linear

than that for O2.

5. The PO2 in some tissues is less than 5 mm Hg, and the purposeof the much higher PO2 in the capillary blood is to provide an

adequate gradient for diffusion. Factors determining O2

delivery to tissues include the blood O2 concentration and the

blood flow.


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X. Mechanisms of Arterial Hypoxemia

What the USMLE expects you to be able to do1. Define the 4 types of hypoxia including arterial hypoxemia and

the expected values of blood gases in each type.

2. Describe the 5 causes of arterial hypoxemia and identify those

that result in a widened (Alveolar-arterial) PO2 difference.

3. Explain why mismatching of ventilation and perfusion affects

arterial PO2 more than arterial PCO2.

4. Describe the effect of gravity on distribution of alveolar ventilation(VA) and blood perfusion (Q) and the ratios (VA/Q) in the normal lung

5. Explain how 100% oxygen can be used to diagnose VA/Q mismatch

and shunt.


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Types of Hypoxia

2. Arterial hypoxia, orhypoxemia:

A) Low inspired PO2 (low PIO2)

B) Diffusion limitationC) Hypoventilation

D) Alveolar ventilation / perfusion mismatch

E) Right to left (venous) shunt

1. Tissue Hypoxia:

a) Stagnant hypoxia

b) Anemic hypoxia

c) Histotoxic hypoxia

Judgment parameters:

PaCO2 and (A a) PO2


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Types of Hypoxia

2. Arterial hypoxia, orhypoxemia:

A) Low inspired PO2 (low PIO2)

B) Diffusion limitationC) Hypoventilation

D) Alveolar ventilation / perfusion mismatch

E) Right to left (venous) shunt

1. Tissue Hypoxia:

a) Stagnant hypoxia

b) Anemic hypoxia

c) Histotoxic hypoxia

Judgment parameters:

PaCO2 and (A a) PO2


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Normal DL

Low DL

Diffusion

limitation

0 0.25 0.50 0.75


PO2(mm

Hg)

0

50

25

Alveolar

exercise rest

Diffusion limitation


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O2 CO2

PIO2 = 150 mmHg

PICO2 = 0 mm Hg

PAO2 = 100 mmHg

PACO2 = 40 mm Hg

Normoventilation

PVCO2 = 45 mm Hg

PVO2 = 40 mmHg

PaCO2 = 40 mm Hg

PaO2 = 90 mmHg


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Hypoventilation

Airway

obstruction

O2 CO2

PIO2 = 150 mmHg

PICO2 = 0 mm Hg

PAO2 = 80 mmHg

PACO2 = 60 mm Hg

PVCO2 = 65 mm Hg

PVO2 = 30 mmHg

PaCO2 = 60 mm Hg

PaO2 = 70 mmHg

Distribution of ventilation and perfusion in the Lung


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I

II

III

p g

in an upright position

(mmHg)

13228

10040

90

42

PCO2

PO2

Q

Perfusion / tissue mass,

I

II

III

A. Perfusion distribution

VA

Ventilation / tissue mass,

B. Ventilation distribution

II

III

I

VA VAVA and Q


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VA

and/or

Q

High

VA and/or

Q

LowVA

Q

: Normal

VA and Q

normal

PA Pa

PI

Pv

160

120

80

40

PO(mmHg)

2

Q

VA

PI

Pv

PA = Pa

Unequal distribution of Ventilation (VA)


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Alveolar

region 1Alveolar

region 2

q ( )

and Perfusion (Q)

AaD

(Alveolar-

arterial

difference)

I

v

PO2

Lung:

Alveolar

Arterial

VA/ Q high:

Hyperventilated

VA/ Q low:

Hypoventilated

PI

Pv

PA1 Pc'1=PA2 Pc'2=

Pa

PA

A2=c'2

A1=c'1


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Right to left shunt(venous shunt)

Hypo-ventilated

Alveolar deadspace ventilation

Hyper-ventilated

"IdealAlveolus

Pv Pa

PI PA

PAi

normoventilated

Average

VA / Q

PI

Alveolardead space

= VA / Q

PI

VA / Q

Pv

Right to leftshunt

= 0

Pv

O2 - and CO2 Binding curves


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43 ml/l

5 mm Hg

CO2

0 20 40 60 80 100

Partial pressure (mm Hg)

600

400

200

0

Concen

tra

tion(ml/l)

O2

RQ =43

50 = 0,86

arteria

l

mixe

dvenous

55 mm Hg50 ml/l

mixe

dvenous

arteria

l

Effects of shunt on arterial PO2 and PCO2


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Effects of shunt on arterial PO2 and PCO2

PA

PvPa

Pc' = PA

Q

Pv

Shunt 25% of Q

2. Advantage for CO2:

Based on very steep slope of CO2 binding curve (in comparison

to that of O2),there is practicaly no shunt effects on PCO2.

PaiCO2 = PaCO2 ist a reasonable assumption


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Normal Unchanged No

Normal Unchanged Yes

Unchanged Unchanged Yes, but be careful

Normal Yes( )

Causes of hypoxemia

and effects of O2

breathing

Increases in

VA/Q heterogeneity

Increases in

Right to left shunt

Diffusion problems

Hypoventilation

PaO2with 100%O2AaDO2 PaCO2 aADCO2PaO2

Low PIO2(high altitude) Unchanged Unchanged Yes

KEY CONCEPTS1 Th f f h i h til ti diff i


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1. The four causes of hypoxemia are hypoventilation, diffusion

limitation, shunt, and ventilation-perfusion inequality.

2. The two causes of hypercapnia, or CO2 retention, are

hypoventilation and possibly ventilation-perfusion inequality .3. Shunt is the only cause of hypoxemia in which the arterial PO2

does not rise to the expected level when a patient is given 100%

O2 to breathe.

4. The ventilation-perfusion ratio determines the PO2 and PCO2 in any

lung unit. Because the ratio is high at the top of the lung, PO2

is

high there and the PCO2 is low.

5. Ventilation-perfusion inequality reduces the gas exchange

efficiency of the lung for all gases. However, many patients with

ventilation-perfusion inequality have a normal arterial PCO2. By

contrast, the arterial PO2 is always low. The different behavior of

the two gases is attributable to the different shapes of the twodissociation curves. In the case of CO2 increased alveolar

ventilation contributes additionally in keeping arterial PCO2 normal.

6. The alveolar-arterial PO2 difference is a useful measure of

ventilation-perfusion inequality. The alveolar PO2 is calculated

from the alveolar gas equation using the arterial PCO2.

XI Control of Breathing


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XI. Control of BreathingWhat the USMLE expects you to be able to do1. Describe the functions of the neural control centers for breathing

including the ventral respiratory group (VRG), dorsal respiratorygroup (DRG) and pneumotaxic center of the brainstem.

2. Explain how a patient with bilateral paralysis of the diaphragm is

able to breathe.

3. Describe the innervation of muscles used for breathing and predict the

effects of spinal cord injuries at different levels on the ability of patientsto breath; e.g., transection at C2 versus transection at C6.

4. Contrast the primary stimuli, thresholds, nerve pathways, and response

times of central and peripheral chemoreceptors.

5. Describe the location and pattern of breathing illicited by irritant and

mechanical receptors.

6. Explain why O2 therapy may decrease breathing in a patient with

chronic obstructive lung disease; e.g., emphysema.

7. Contrast the acute vs. chronic effects of hypoxia and hypercapnia

on ventilation. Describe the functions of the neural control centers for

breathing.

Respiratory center & afferent and efferent inputs


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Rhythm generator

Chemoreceptors

Mechanoreceptors inlung and thorax

With feedback

Respiratory stimuli:

Without feedback

Mechanoreceptors inmuscloskeletal system

Afferent

inputRespiratory

muscles

Efferentoutput

Brainstem(Emotion,Temperature)

Cortex(exercise, voluntary)

Centralinput


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VRG

Pons

Medulla

3 groups of neurons control

respiration

DRG

(NTS)

Pneumotaxic

Center

Inhibitory effects:

Off switch of

inspiration, control

of FR

Basic rhythm Cardiorespiratory, symp.

and parasymp. coupling

Basic activity of bronchial

muscle cells

Extra drive: exercise, high

altitude

Integration

of inputs

Vagus &

GlossopharyngealRespiratory

Motor Paths

Basic

rhythm

ramp signal


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Pulmonary Reflexes:

1. Slowly Adapting Stretch Receptors (Hering-Breuer reflex):

Location: Airway smooth muscles, innervated by large myelinated

vagal fibers

Activation:a) Lung distension (inspiration)

b) Breath holding (lack of movement)

c) Deflation of the lung below FRC

Functions:a) Terminates inspiration (prevent the lung from

overstretching)

b) Terminates large expiration as well

Lung stretch reflex


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Lung distensionInspiratory

muscles

Rhythm generator

(Respiratory center)

+

+

-

Lung stretch reflex


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2. Rapidly Adapting Stretch Receptors (irritant

receptors):

Location: Airway epithelium, innervated by myelinated vagalfibers

Activation:a) Lung distension

b) Irritants

Functions:a) Cough reflex

b) Gasp and bronchoconstriction by high activity


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3. C-Fiber or J-Receptors (J = Juxta capillary):

Location: Near capillaries, innervated by non-myelinated vagalfibers

Activation:a) Increases in interstitial fluid (congestion or edema)

b) Pulmonary embolism

Functions:a) Rapid shallow breathing

b) Bronchoconstriction

c) Cardiovascular depression


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Peripheral chemoreceptors


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External carotid arteryInternal carotid artery

Carotid sinus

Left subclavianartery

Common carotidartery Brachiocephalic

trunk

Aortic arch

Pulmonal artery

N.IX (Glossopharyngial nerve)

N.X (vagus nerve)

Aorticbodies

Carotidbody

Peripheral Chemoreceptors


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Carotid body(glomus caroticum)

Carotidsinus

nerve

Capillary

Type I cell

Type II cell

Mechanism of Peripheral Chemoreception


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Type I cell

Actionpotential

Transmitter

release

pH

O2

PCO2

pHi

K+ Outflux

Cai2+

Depolarization Ca2+ Influx

p p

O2 response curve


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At PaCO2 = 40 mmHg

Value at rest

By falling PaCO2

Arterial PO2 (mmHg)

0 30 60 90 120 150

40

30

20

10

0

Minu

teven

tila

tion(lm

in-1)


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Chemical stimuli of breathing

PaCO2 falls

7,4 7,3 7,2

pHa

B: pH response curve

Normal

30 60 90 120 150

PaO2 (mmHg)

PaCO2 constant

PaCO2 falls

C: O2 response curve

Normal value

A: CO2 response curve

Normal value

30 45 60 75

PaCO2 (mmHg)

60

80

40

20

0

Minu

teven

tila

tion(l/min)

PaCO2 constant

Acute vs. chronic hypercapnia


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CSF and blood pH = HCO3-

PCO2PCR &

CCR stimulated

20

Ventilation

Time, days

PCO2

Only PCR

stimulated

Acute vs. chronic hypoxia


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Days

Alkalosis from hyper

ventilation inhibits

response to hypoxia duringfirst few days

Stimuli for ventilation

Voluntary control


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Voluntary control

0

20

40

60

80100

120

140

160

Rest PO2 pH PCO2 Exer MVV

Ventilation,

L/min

Maximum VE response to stimuli

Regulation of breathing during exercise


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Musculoskeletal system

workingmuscles

Cerebral cortex

motor

Rhythmgenerator

Respir.muscles

Mechanoreceptors

sensory

"direct stimulation"

Stimulation throughfeedback"

Abnormal Patterns of Breathing


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g

Sleep Apnea

Abnormal Patterns of Breathing


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Cheyne-Stokes Breathing

KEY CONCEPTS1. The respiratory centers that are responsible for the rhythmic pattern of


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breathing are located in the pons and medulla of the brainstem. The output

of these centers can be overridden by the cortex to some extent.

2. The central chemoreceptors are located near the ventral surface of the

medulla and respond to changes in pH of the CSF, which in turn are causedby diffusion of CO2 from brain capillaries. Alterations in the bicarbonate

concentration of the CSF modulate the pH and therefore the chemoreceptor

response.

3. The peripheral chemoreceptors, chiefly in the carotid bodies, respond to a

reduced PO2 and increases in PCO2 and H+ concentration. The response to O2

is small above a PO2 of 60 mm Hg. The response to increased CO2 is lessmarked than that from the central chemoreceptors but occurs more rapidly.

4. Other receptors (mechano-and irritant receptors) are located in the walls of

the airways and alveoli.

5. The PCO2 of the blood is the most important factor controlling ventilation

under normal conditions, and most of the control is via the central

chemoreceptors.

6. The PO2 (above 60 mm Hg)of the blood does not normally affect ventilation,

but it becomes important at high altitude and in some patients with lung

disease

Documents

Respiration Part 2, Lectures 8 to 14, Jan 2011