Respiratory Physiologyclinsoft.org/drmayrovitz/PHYSIOLOGY/RESPIRATION/COM...2 x P ATM = 0.21 x 760 = 159.6 →160 mmHg Q T = Volume/breath x Respiratory Rate Q T = Tidal volume x RR

Respiratory Physiology

Dr HN Mayrovitz

Harvey N. MayrovitzRoom 1313

e-mail: [email protected]: drmayrovitz.com

1. 9/13 11-12

2. 9/16 1-2

3. 9/16 2-3

4. 9/17 10-11

5. 9/17 11-12

6. 9/20 10-11

7. 9/20 11-12

8. 10/2 8-9

mailto:[email protected]

• The objectives have been better defined for a more detailedand easier interpretation. These will appear before each lectureand supersede any prior listing.

• My exam questions will be based on the objectives as reflected bymaterial presented in lecture via slides and discussion

• I provide a “handout” with additional words that might be usefulfor some. It covers more topics than will be presented.

• If we fail to complete the material for a given lecture the planis to finish on the next lecture

• After-lecture questions if “short” usually can be handled via emailOtherwise we should plan on scheduling one-on-one time byappointment via email contact for mutual availability

Preliminaries

Dr. HN Mayrovitz

Lecture 19/13/19

Respiratory Design andStructure-Function

Dr HN Mayrovitz

Eastman Kodak 1937

Heart Shadow

Lung Shadow

OBJECTIVES

To describe and explain the following elements of respiratory physiology

• Physical aspects of oxygen and carbon dioxide dissolution in blood

• Concepts of dead space and its calculation

• Concepts total and alveolar ventilation and their calculation

• Factors affecting lung fluid exchange and its calculation

• Pulmonary blood flow and factors and processes that affect it

• Basic aspects of respiratory control processes

Trachea

Thorax

Lung and

the Alveoli

Simple BreathingModel

Dr HN Mayrovitz

P

Trachea

Thorax

Lung and

the Alveoli

AirAir ~ 21% O2

755 mmHg

760 mmHg

At end ofExpiration

Dr HN Mayrovitz

blood

PO2 = 100 mmHg

Dissolved O2

[O2] = 0.3ml/dl

[O2]d = KO2 x PO2

K = solubility= 0.003 mlO2/

ml/mmHg If CO = 6 L/min

O2 delivered= 60x 0.3= 18 ml O2/min

Only 18ml/300ml~ 6% of needed

O2

Gas Basics: O2 Dissolved in Blood

1/18 Dr HN Mayrovitz

PO2 = 100 mmHg

Hb4O2

O2

O2

O2

@100% Saturation

(34 g/Hb/100 ml rbc) x Hct34 x 0.44 = 15 gHb/100 ml blood

O2

Hb O2 binding capacity ~ 1.34 mlO2/gHb

15 x 1.34 = 20.1 mlO2/dl

Normally 97% sat

0.97 x 20.1 = 19.5 mlO2/dl

+ 0.3 ml dissolved

~ 20 mlO2/dl

Gas Basics: O2 Bound to Hemoglobin in RBC

O2 Bound to Hemoglobin

in RBC


Gas Basics: Carbon Dioxide

blood

PCO2 = 40 mmHg

Dissolved CO2

[CO2] = 2.4ml/dl

[CO2]d = KCO2 x PO2 = 2.4 ml/dl

K = solubility= 0.06 mlCO2/

100ml/mmHg CO2

As BicarbonateHCO3 →90%

CO2 in Blood48 ml/dl

2.4/48 →5%

Carbon Dioxide@ PCO2

of 40 mmHg


NoseMouth

Trachea

Bronchi

Bronchioles

T.Bronchioles

ConductingZone

No GasExchange

Dead Space

Ventilation

Perfusion

Diffusion

Respiratory ZoneGas

Exchange

Transition Zone

Alveoli

0

1617

23

Respiratory Bronchiolesand Alveolar Ducts

0.5 mm thick

Airways and Alveoli Schematically Summarized

Dr HN Mayrovitz4/18

MixedVenousBloodFrom RV

Upper Airways(Conducting zone)

(Anatomical Dead Space(ADS)

TotalVentilation

(QT)

Respiratory zone

Alveolar Ventilation

Blood Perfusion

Respiratory Processes: Ventilation-Perfusion-Diffusion

Gas Diffusion

ArterializedBlood to LA

[O2] = 0.21 → FIO2

[CO2] = 0%[N2] = 0.79

PATM=760 mmHg

PO2 = FIO2 x PATM = 0.21 x 760 = 159.6 → 160 mmHg

QT = Volume/breath x Respiratory RateQT = Tidal volume x RR = TV x RR

QA = (TV – ADS) x RR

PO2 = (PATM – 47)FIO2 149.7 → 150 mmHg

PO2 = 40 mmHgPCO2 = 46 mmHgSO2 = 75%

PO2 = 100 mmHgPCO2 = 40 mmHgSO2 = 97.4%

Gas fractionsat sea level

Dr HN Mayrovitz

5/18

Capillary Blood Flow(Perfusion)

Alveolar Gas VolumeEntering and Leaving

Per Breath = VA

Arterialized BloodExiting Lung to LA

MixedVenousBlood

from RV

PCO2 = 40

Dr HN Mayrovitz6/18

• Collect one TV of expired air• Measure CO2 fraction (FECO2)

(1) CO2 volume = FECO2 x TV

CO2 source is volume from alveoliduring that tidal volume

CO2 from alveoli is(2) FACO2 x VA

Alveolar Dead SpaceVentilation but No Perfusion

Dead Space: Physiological = Anatomical + Alveolar

(3) FECO2 x TV = FACO2 x VA

VDCO2 = TV(PACO2 - PECO2 ) / PACO2

Physiological Dead Space

Interpret If: PACO2 = PECO2

Interpret If: PECO2 = 0

Alveolus

Type II Cell

Fluid withSurfactant

Type ICell

Capillary

MacrophageO2

Alveolar Cells and Capillaries

CO2

Dr HN Mayrovitz7/18

Capillary

Alveolar Inward Forces

SurfaceTensionForces

ElasticRecoilForces

Dr HN Mayrovitz8/18

rbc

AlveolarEpithelium

InterstitialSpaceCapillary

Endothelium

O2

0.1mm

Ca

pill

ary

Gas Exchange Interface

CO2

Alveolus

Dr HN Mayrovitz9/18

Visceral

Pleura

Intrapleural

Space

Pulmonary

Capillary

LUNG

Systemic

Capillary

Parietal

Pleura

Chest

wall

Intrapleural Space (simplified)

Dr HN Mayrovitz10/18

P = 10

P = 25

P=15

P=5

Alv

eo

lus

Lymphaticdrainage

8

pulmonary

capillary

visceral pleura

PulmonaryInterstitium

ProteinLeak

P = -2

P = 17

s~

0.5

Pulmonary Fluid Balance

Pressures in mmHg

DPeff = TMP –s DP = [10 –(-2)] – 0.5 (25-17) = 8


systemic

capillary

P = -5

P = 7P = 10

P = 25P = 25

P = 25

7 12

Small enough volume to maintain cohesive force

Just large enough volume to provide lubrication

P=15

P=5

P=35

P=15

Parietal pleura

intrapleural

Alv

eo

lus

Lymphaticdrainage

8

Route forAlveolarFlooding

InterstitialEdema

PleuralEffusion

Filtration

Pressure

Lymphatic drainage

pulmonary

capillary

visceral pleura

PulmonaryInterstitium

ProteinLeak

P = -2

P = 17

s~

0.5

Pressures in mmHg

Pulmonary Fluid Balance DPeff = TMP –s DP = [10 –(-2)] – 0.5 (25-17) = 8


Cervical

ganglion

Vagus n.

Pulmonary

plexus

Pons

Medulla

Phrenic n.

Intercostal n.

Sympathetic Chain

Respiratory Muscles

Airways

Some

Symp

Blood

Vessel

Control

+Vagus =AW constrict

Neural: Muscles

Diaphragm

Dr HN Mayrovitz

Forced inspirationor expiration

13/18

Cervical

ganglion

Vagus n.

Pulmonary

plexus

Pons

Medulla

Phrenic n.

Intercostal n.

Sympathetic Chain

Respiratory Muscles

Airways

Some

Symp

Blood

Vessel

Control

+Vagus =AW constrict

Neural: Muscles and Airways

Diaphragm


Systemic

Pulmonary

LV

LA

RA

RV

RVPressure

Pulse

FlowPulse

LV PressurePulse

FlowPulse

PV

(2)

25/0

120/0

24/9

(93)

(14)→(12)→→→9

DP=5

0

25

0

120

120/80DP=91

Pressures (mmHg)Mean Values ( )

•Low Pressure•High Flow ~ CO•Low Resistance~ 10-12 %

Blood Volume

(8)

Pulmonary Pressure and Flow Features


Ventilation Control

RespiratoryMuscles

Brain Stem• Pons • Medulla

Lung and

Thorax

Rhythmic Impulses

Inspiration/Expiration

Tidal Volume (TV)Respiratory Rate (RR)

VENTILATION

Central

Chemoreceptors

Peripheral

Mechanoreceptors

Stretch

HigherBrain

CenterspH & CO2

O2

CO2 & pH

Lung volume changes

NormalEupneicBreathing

Inspiration Expiration Inspiration


RightSide Brachio-

cephalic

X

CommonCarotids

Aorta

AorticBodies

XExternalCarotid

CarotidBody

IX

Hering n.

MedullaryRespiratory

Center

Aortic n.

Peripheral Chemoreceptor Locations


Vagus

(glosssopharyngeal)


TidalVolume

TV = 500 ml QT = Total (minute) Ventilation

QT = RR x TV = 6000 ml/min

RR = Respiratory Rate = 12/min

AlveolarGas Volume

AnatomicDead SpaceADS=150 ml(~1 ml/lb)


PO2 = 40SO2 = 75%PCO2= 46

MixedVenousBlood

from RVPO2 = 100SO2 = 97%PCO2= 40

QA=Alveolar Ventilation

QA = (TV - ADS) RR

QA = (350 X 12)

= 4200 ml/min

PO2 = 102 PCO2 = 40

PO2 = 160 → Partial Pressure (mmHg)

PCO2 = 0.3 760 x 0.21 = 159.6

Main Respiratory Function: Review


End Lecture 1

Dr HN Mayrovitz

Lecture 29/16/19

Lung Volumes and Pressures

Dr HN Mayrovitz

OBJECTIVES


• Lung volumes and capacities and how to calculate capacity from volumes

• The methods used to measure lung volumes and capacities

• Calculation of lung volumes from helium dilution

• Calculation of lung volumes from whole body plethysmography

• Respiratory pressures and how these are determined and used

Pulley

Bell

H2O

RotatingDrum

Volume Measurements - Spirometer

pen

Doublewalleddrum

Inspiration

Up with Inspiration

Dr HN Mayrovitz1/16

FRC3.0

VC4.2 TV

0.5

RV

IRV2.5IC

3.0

TLC6.0

EndInspiration

EndExpiration

TidalVolume

Maximum Inspiratory Level

ERV1.2

Residual VolumeRV1.8

Lung Volumes and Capacities

Maximum Expiratory Level

“Equilibrium”at FRC

Dr HN Mayrovitz2/16

KNOW ABREVIATIONSTV = Tidal VolumeIRV = Inspiratory reserve volumeERV = Expiratory Reserve VolumeRV = Residual volumeIC = Inspiratory CapacityFRC = Functional Residual CapacityVC = Vital CapacityTLC = Total Lung Capacity

Spirogram up is inspiration

O2

10% He

soda

lime

He

FRC & RV via Helium Dilution→ Start

Assume

3000 ml total

10%

0%

Start breathing gas at FRC

0%

Before starting test

He concentration in spirometer = 10%

close

open

Dr HN Mayrovitz3/16

At Equilibrium → End

He

5%

5%

He Concentration

Measured

He concentration

In lung = 5%

He concentration in lung & spirometer = 5%

Dr HN Mayrovitz4/16

Calculations

Initial He volume = Final He volume

He in lungs + He in spiro = He in combined (lung + spiro)

Start End

0 + 0.10x3000 = 0.05 (FRC + 3000)

RV = FRC - ERV

Measured

by SSCalculated

VL & FL are Volume & Fractional Lung concentration

Vsp & Fsp are Volume & concentration in Spirometer

FRC = 3000

VL x FL_start + Vsp x Fsp_start = (VL + Vsp) FL_end

FL_end = Fsp_end

Dr HN Mayrovitz5/16

FRC by Body Plethysmography

Airway

Pressure

Box

Pressure

Shutter

closes

at end of

expiration

Eupneic

Breathing

Lung volume

at end of

Expiration = FRC

1

2

Air Tight Chamber

Dr HN Mayrovitz6/16

p’=palv

At end of expiration

p=palv=patm

V is unknown

Inspiration

•Thorax enlarges

•Gas decompresses

•Volume increases

V’ = V + DV

•Pressure decreases

p’ < p

Box Pressure

increases

DPbox=kDV

Boyles Law: p V = p’ ( V + DV )

p p’

DPbox/K

Shutter

closed

V = FRC

Air Tight Chamber

Lung

Inspire with shutter closed

FRC by Body Plethysmography

Dr HN Mayrovitz7/16

He dilution (and N2 washout) methodsmeasure COMMUNICATING GAS VOLUME

Lung gas that can mix with the breathing mixture

Body plethysmographic methodmeasures TOTAL gas volume

Gas that is or is not in communication with alveoli

Method Comparisons

Both methods require good patient compliance

Dr HN Mayrovitz8/16

Pressures

Air

PALV

PREC

PREC

Elastic SurfaceTension

At any specific volumePALV = PREC

PALV

Volume

Alveolar and Recoil Pressures

Dr HN Mayrovitz9/16

PALV

PREC

PALV = PREC + PE

PE

To maintain the same sizePALV must change by PE

PALV – PE = PREC

If PE is intrapleuralPressure PPL then

PALV = PREC + PPL

Enter Intrapleural Pressure


PREC

PTH

PPL

Chest WallRib Cage

1. RespiratoryMusclesExpand

Wall

2. IntrathoracicPressure (PTH)decreases

3. Pleural spacetries to enlargecausing PPL to decrease

4. PALV = PREC + PPL

decreases

5. Air is drawn in Q = PATM - PALV

PALV

Inspiration → Air Flow


PATM = 0

PREC

Diaphragm

Intrapleural

(PPL)

Parietal

Pleura

Ribs

(chest

wall)Alveolus

Intrapleural space (fluid)

Alveolar

(PALV)

Pressure Summary

Chest

Recoil

Lung Recoil

(PREC)

PALVPALV = PREC + PPL

Visceral

Pleura

Lung

recoil

PTH

Intrathoracic (PTH)

PALV = PREC + PTH

Airway (PAW)

PBS


PATM = 0

PREC

PPL

PBS

Trans-Airway

Pressure

(PAW - PPL)

PPL

PALV

2

PTL is the pressure that serves to expand alveoli

PTW

3

If PBS =0

PTW = PPL

Total Respiratory

System Pressure

PRS = PTL + PTW

4

Trans-Lung Pressure

PTL= (PALV - PPL) = PREC

= (PALV - PTH)

1

Transmural Pressures: Total Respiratory

Trans-Wall

Pressure

(PPL- PBS) PRECwall

Dr HN Mayrovitz

Lung

PPL = -5 (assumed)

PATM = 0

PREC

(+5)

PPL

Pressure: NO AIRFLOW: End Expiration

Recoil balances PPL

PALV=(PREC+ PPL) = 0

= 5 + (- 5)

Volume Fixed

1. Under no flowconditions (Static)PALV must = PATM = 0

PTL= PALV – PPL = 0 – (-5) = +5

2. Volumeis determinedby PTL alongwith lungcompliance

PALV

Dr HN Mayrovitz

14/16

Lung

PPL

PATM = 0

PREC

PPL

PALV=(PREC+ PPL) = 0

= 8 + (- 8)

Volume Fixed

3. To sustain thenow larger volumePPL is more neg and is again balancedby the recoil pressure, PREC

PALV

Volume

PREC

PTL= PALV – PPL = 0 – (-8) = +8

Pressure: NO AIRFLOW: End Inspiration

Dr HN Mayrovitz

15/16

0 1 2 3 4Seconds

Intrapleural-5

-8

cm

H2O

Inspiration Expiration

Q (l/sec) has same form as PALV

-2.5

+2.5

Dynamic Pressure and Flow Changes

PPL

Air Flow depends onthe difference between alveolar pressure andatmospheric pressure

Q ~ PATM - PALV

in

out

Air flow is zero twice during cycleIf Q=0 PALV = PATM

Change in lung volume

cm

H2O

PALV

0

0.5

L

Alveolar

Dr HN Mayrovitz

16/16

End Lecture 2

Dr HN Mayrovitz

Lecture 39/16/19

Compliance and Resistance

Dr HN Mayrovitz

C = DV/dP

R = DP/Q

OBJECTIVES


• Respiratory compliances (lung, thoracic and total) and their determination

• The physical factors that affect these compliances

• The overall respiratory system pressure-volume relation and its interpretation

• The concepts of elastic and inelastic energy and their graphical interpretation

• The Valsalva maneuver and its respiratory and cardiovascular effects

• Airflow and airway resistance within the pulmonary tree

• Calculation of resistance and flow in collapsible airways

• Vascular resistance changes due to changes in lung volume and gravity

Vo

lum

e (

V)

Transmural Pressure (dP)

dP

DV

DV

dP

Larger dP for thesame DV thus

less compliance

Slope of P-V curveis DV/dP which isCompliance

Compliance

Pin

Pout

dP = Pin - Pout

dPC =

DV

Dr HN Mayrovitz1/18

0

50

100

0 +10 +20 cmH2O Translung (Transpulmonary) Pressure

LungVolume(% TLC)

open closed alveoli against surface tension

FRC

TV

Low C

Lung Pressure-Volume Relations

DynamicStatic

Lung

Only

Dr HN Mayrovitz2/18

0 10 20 Translung Pressure (cm H2O)

Lung ComplianceC = DV/DP

= 0.5L / 2.5 cmH2O= 0.2 L / cmH2O

2500

3000

Expand

5 7.5

Vo

lum

e (

ml)

Lung ComplianceReduced Compliance• Scarring• Fibrosis• Edema• Reduced surfactant

FRC

• Surface Tension = T causes inward pressure P = 2T/r• T is reduced by presence of lung surfactant (LS)

T

Effects of Lung Surfactant1. Increases Compliance2. Reduces tendency for closure (atelectasis)3. Reduces tendency for alveolar capture4. Reduces tendency for fluid transudation

Alveoluspictured

as a Soap

Bubble rP

T

Dr HN Mayrovitz3/18

0 -2.5 -5.0 -7.5 cmH2O PPL

0 +2.5 +5.0 +7.5 cmH2O PTL

2500

3000

Elastic vs. Inelastic Work

Work to overcomepure elasticity

WE ~ ½ DV x DP~ 250 x 2.5

Work to overcome

AirwayResistance

Work toovercome

tissueviscosity

Elastic ~ 2/3 Inelastic ~ 1/3

4/5

1/5ml DV

DP

A

B

Dynamic LoopArea ~ Energy Loss

Dr HN Mayrovitz4/18

Lung and Chest Wall Forces

•Lung Elastic Forces:tend to close the lung at any lung volume

At FRC: Forces are equal but oppositely directed

Inspiration: Lung force Chest force

At ~70% TLC: Chest force = 0 (at 0 stress position)

•Chest Wall Elastic Forces:tend to expand lung for most lung volumes

> ~60-70% TLC: Lung & Chest forces tend to close lung

Lung + Thorax Interactions DetermineRespiratory System P-V and Compliance

Dr HN Mayrovitz5/18

Lung and Thorax as Springs

LungsAlone

ThoraxAlone

Lungs+Thoraxheld

togetherby pleuralsurfaces Air

Pneumothorax

TLC

100%

FRC~50%

RV

LungRecoil

ChestRecoil

<RV

>FRC

IntrapleuralPressure

~70%

0 mlA B C D

Dr HN Mayrovitz6/18

-10 -5 0 5 10 15 20 25 30

Recoil Pressure (cm H2O)+ is direction to reduce volume

Volume%TLC

Chest Expands

PRECW

Lung ExpandsPRECL Increases

Respiratory System PRS = PTL + PTW = PALV

FRC

Respiratory System P-V relations

Chest Outward Recoil

ChestInwardRecoil

50%

70%

Lung Recoil is + at all lung volumes

ChestNo Recoil

PRS = 0 @ FRC

PRS = PTL All recoil Is due to lung

PREC

PTM

PTLPTW

Dr HN Mayrovitz

7/18

1/CRS = 1/CL + 1/CW

CL ~ CW = 0.2 l/cm H2O

CRS = 0.1 l/cm H2O

0 10 20 30 40 50

Surface Tension (dynes/cm)

100

75

50

25

0

Area

%

Normal

Lung

Extract

Respiratory Distress Syndrome

Deflation: Low surfactant

• Normal decrease in surface tension not present

• Greater force at any alveolar volume acts to close alveoli

Newborn succumbed

to RDSLung

extract

Inflation: Once closed:

• Big work/breath neededto re-inflate lungs

• Increased muscular workfatigues diaphragm

T

Dr HN Mayrovitz8/18

-100 -80 -60 -40 -20 0 +20 +40 +60 +80 +100

0

100

RV

Valsalva maneuverForced EXPIRATION

against closed glottis

Expiratory Effort

FRC

Muller maneuver

Inspiration against

closed glottis

Inspiratory Effort

Forced Expiration at

different lung volumes

Forced Inspirations at


Insp

ire t

o s

om

e v

olu

me

Max PALV

Higher Negative Pressures

At lower volumes

% o

f V

ital

Cap

acit

y

Total Respiratory Pressure (PRS) = Alveolar Pressure

Muller and Valsalva ManeuversLarge Pressures Associated with Active/Forced

Inspiration/Expiration

Dr HN Mayrovitz

9/18

-100 -80 -60 -40 -20 0 +20 +40 +60 +80 +100

0

100

RV

Valsalva maneuverForced EXPIRATION

against closed glottis

Expiratory Effort

FRC

Muller maneuver

Inspiration against

closed glottis

Inspiratory Effort

Forced Expiration at


Forced Inspirations at


Insp

ire t

o s

om

e v

olu

me

Max PALV

Higher Negative Pressures

At lower volumes

% o

f V

ital

Cap

acit

y

Total Respiratory Pressure (PRS) = Alveolar Pressure

•Straining at stool

•Childbirth

•Weight lifting

Large (+) Pressures•Lung rupture danger•Aortic → +BP→-HR•Vena Cava → - VR

Large (-) pressures cause large blood vessel transmural pressureHemorrhage danger

Muller and Valsalva Maneuvers – Potential Dangers


Phase I: (Onset of strain)a) +PTH & +PAB → +BP (A & V & chambers)b) Baroreceptor mediated – HRc) MBP begins to fall

Phase II: (continued strain & pressure recovery)a) SVC compression → - Venous return → - SVb) Further decrease in MBP (systolic & PP)c) Decreased BP → +SYMP → +TPR & +HRd) BP recovery (above baseline)

Phase III: (Release)a) Normalized PTH

b) Transient precipitous -BP with reflex +HR

Phase IV: Recoverya) Venous return back to normal → + SV → +COb) +CO combined with prior +SYMP → BP overshootc) Baroreceptor reflex rapid -HR

Phase: I II III IV

0 10 25 sec

Valsalva

MBP

HR

Valsalva Maneuver – CV Effects (basic)

“Typical” Featureswith Valsalva initiatedfrom a normal inspiration


Valsalva – Clinical Correlation

63 year male → Normal

56 year male → Autonomic Neuropathy


Valsalva

Valsalva

HR

(b

pm

)H

R (

bp

m)

BP

(m

mH

g)B

P (

mm

Hg)

Time (sec)

Airway Flow Features and Resistance

DP = K2Q2

Turbulent

DP = K1 Q + K2Q2

Bronchial Tree

DP= K1Q

Laminar


Intra-alveolar

With inspiration PPL

decreases causingvessel widening

PTM = PA - PPL

R

Extra-AlveolarBlood vessels

Expanded alveolicompress capillaries

R

Alveolus

Alveolus

Alveolus

PA

©Dr. HN Mayrovitz 2011

Extra-alveolar Intra-alveolar

Lung Volume Affects Vascular ResistanceOpposite effects of intra and extra alveolar vessels


Total Vascular Resistance

Extra-Alveolar

Alveolar

Total R = Alveolar R + Extra-Alveolar R

RV FRC TLC

Vas

cula

r R

esi

stan

ce

Minimum at About FRC


Gravity Affects Vascular Resistance

12 mmHg16 cmH2O16 cm

16 cm

P=16-16=0 cmH2O

P = 16+16 = 32 cmH2O

PulmonaryArteriole

Blood Flow Distribution

Base Apex

Simplified main concept

Flow

At Base: - TMP Greater- Vascular Resistance Less- Blood Flow is Greater

Apex


Pa>PA>Pv

PA>Pa>PvI

II

III

PA

Pv

Pa>Pv>PA

Alveoli Dead space (ventilated but not perfused)

Uneven Blood Flow: The Zone Model

Pa

± 2.5

Blood Flow

Q=(Pa-PA) / Rx

I

II

IIIQ=(Pa-Pv) /RT

~Uniform with depth

Pa Increaseswith depth

R decreaseswith depth

if Pa abnormally low

0 maxDr HN Mayrovitz17/18

Pu PdP1 P2Q

Pe

Increase P1 – P2 but hold P1 – Pe constant

1. Fix P1 - Pe & lower P2 (~cvp decrease with + CO)

2. Fix P2 & raise P1 & Pe equally (~ forced expiration)

Same result: Q increases as P1 - P2

increases until PTM becomes critical

and buckling starts. Now Q depends

on P1 – Pe not on P1 – P2.

Rigid

Closed chamber

with external pressure

Collapsible tube in chamber. Connected

to upstream and downstream reservoirsRigid

Pi

If Pi < Pe at any point then Q ~ (P1- Pe)/Rx

Rx

Air Flow in Collapsible Airways

Flow Limiter“Check Valve”

EPP: Pi = Pe

P1 → PALV Pi→ PAW Pe→ PPL

PALV - PPL

Rx

Equal Pressure Point

Remember me?


End Lecture 3

Dr HN Mayrovitz

Lecture 4 9/17/19Obstructive and Interpreting Pulmonary

Function Tests

Restrictive Disease

Dr HN Mayrovitz

OBJECTIVES

To describe, explain and interpret the following aspects of respiratory physiology

• Dynamic compression and the concept of Equal Pressure Point (EPP)

• Features of obstructive and restrictive lung disease

• Concept of Flow-Volume and Volume-Time graphics

• Pulmonary function tests and their utilization

• Breathing pattern changes associated with obstructive and restrictive disease

• Neural pathways associated with control of airway smooth muscle

A. Small intrapulmonary airways are distensible and compressible. Held open by combination of: (1) Airway transmural pressure (P) and (2) TRACTION by attachments to surrounding tissue.

B. During a forced expiration, PPL becomes + causing pressure surrounding someairways to become greater than pressure inside.

C. This collapsible condition causes airflow to be determined mainly by PREC alone which itself decreases with lung volume.

D. As volume falls so does PREC ultimately causing airway closure. Net result: Nofurther volume can be expelled. This occurs in normal lungs at low volumes. In obstructive lung conditions the volume at which closure occurs is larger.

Dynamic Compression-Airway Closure: Basic Concept

Airway

P

Traction15

0

10

13

10

7

10

10

Alveolus

Airway

15

0

10

13

10

7

10

10

Q Q = PREC

RAW

A B C D

PRECPREC

Dr HN Mayrovitz

Q = PALV - PATM

RAW

15

0

10

13

10

7

10

10

PPL

Q = PALV - PPL

RX

Q = PREC

RX

PALV = PREC + PPL

Collapsible Airway

RX

EPP

Dynamic Compression Summary and ExampleNormally

PPL

PALV

PATMQ

PPL

PAW = PALV - QR

Rx

15

10

0

1. PPL becomes +

2. Pressure surroundingairways is ~PPL

3. PALV = PPL + PREC

10

Q

Dr HN Mayrovitz2/16

PPL

PALV

PATMQ

PPL

PAW = PALV - QRx

Rx

15

10

0

Forced Expiration Events

1. PPL becomes +

2. Pressure surroundingairways is ~PPL

3. PALV = PPL + PREC

10

Dr HN Mayrovitz3/16

Lung Volume (liters)

12

0

TLC RV

LargeAir

Ways

SmallAir

WaysAir

Flo

w (

l/se

c)

EPP moving toward alveolus

Equal Pressure Point (EPP)Enters Small Airways

Airflow now depends on PRECOIL that is decreasing with

decreasing volume

Forced Expiration: Role of EPP

Dr HN Mayrovitz4/16

Lung Volume (liters)

Q =

Air

Flo

w (

l/se

c)

12

0

TLC RV

Start by inspiring to TLC then force air out with sustained effort

maxQ

VOL

PREC

RAW

PPL exceeds PAW

Q ~ PREC / R

Q ~

(P

REC

+PP

L)/

RA

WT

As V further

reduces, PREC

falls more &

R increases.

Flow

Ceases

maxQ=PEFR Max

Effort

Least Effort

Less Effort

Forced Expiration Flow-Volume Summary

Dr HN Mayrovitz5/16

Obstructive and Restrictive Lung Diseases

Basic Concepts

Obstructive = Abnormal Increase in R

Restrictive = Abnormal Decrease in C→ More difficult to expand→ Greater recoil force

Could have combinations – mixed disease

Dr HN Mayrovitz6/16

Obstructive Diseases: Increased Airway Resistance

• Asthma:

Bronchoconstriction – Mucus - Inflammation

• Chronic Bronchitis:

Mucus and inflammatory processes

• Emphysema

Airway lumen reduction due to wall thickening & mucus

Collagen deposition (fibrosis)

Hyperplasia of mucous-secreting glands

Hyperplasia of mucous-containing airway epithelial cells

Airway lumen reduction due to loss of tethering support*

*Elastic tissue lost-traction force less

So … Airways narrowed & reduced in number

**In emphysema: Alveolar tissue loss - Air space increaseLungs more compliantExpiration more difficult - low recoil Dr HN Mayrovitz

Restrictive Diseases: Restricts Lung Expansion

Pleural → Scarring or Effusion or fibrosis etc

Alveolar → Edema or Hemorrhage

Interstitial → Interstitial Lung Disease or Fibrosis

Neuromuscular → ALS or Myopathy

Thoracic/Extra-thoracic →Obesity or Ascites

“PAINT”

SITE → CAUSES

•Interstitial Fibrosis+ alveolar fibrous tissueLung becomes stiffer (-) complianceInspiration more difficult

• Allergic AlveolitisAlvoli Wall Thickens (-) compliance

• Pleural EffusionIntrapleural Fluid buildup: (-) compliance

Pleural fibrosis & + rigidity: (-) compliance

Dr HN Mayrovitz8/16

0 10 20 30Translung Pressure (cm H2O)

Volume

% of

“normal”

TLC

30

50

100

140

Emphysema -

Normal

Fibrosis

High C and Low Recoil

Low C High Recoil

NormalFRC

•Vascular Engorgement•Lung edema•Atelectasis•Low surfactant

DecreasedCompliance

Compliance Abnormalities

Alveolar tissue loss

Dr HN Mayrovitz9/16

0 -2.5 -5.0 -7.5 Intraplerual2500

3000

Normal

RestrictiveDisease

ObstructiveDisease

Lung Disease Increases Dynamic Work

TV

0 +2.5 +5.0 +7.5 TranslungcmH2O


Air

Flo

w (

l/se

c)12

0TLCE TLCA RVETLCN RVN RVRTLCR

Normal

RestrictiveEmphysema(obstructive)

- Elastic-AW traction+ AWRAW close athigher VL

Larger RV

Forced Expiratory Flow-Volume

Asthma

+AWR

RVA

N=NormalE=EmphysemaA=AsthmaR=Restrictive

PREC

RAW RAWPREC

Decreasing Lung Volumes Dr HN Mayrovitz

TLC

PEFR

RV

PIFR

Forced Expiration

Forced Inspiration

PREC

RAW

Force

Lung Chest

VS.

PIFR DETERMINANTSFRC

Complete Flow-Volume Loop


RV

TLC

0 1.0

Time (sec)

Lung

Volume

(liters)

Forced

Vital

Capacity

(FVC)FEV1

Forced Expiratory Volume-Time Test

FEV1 = Forced Expiratory Volume after 1 sec

FEV1 FVC

Forced Vital

Capacity

FEV1/FVC = 0.8NORMAL

Seconds

Factors and Reference Ranges for “Normal”• Gender →Male > Female• Age → Younger > Older• Height → Taller > Shorter• Race → Caucasian>Hispanic>African A.


FVC

Lung Volume

Air

Flo

w (

l/se

c)12

0

TLC RV

LargeAir

Ways

SmallAir

Ways

FEV1

Indicator of smallairway obstruction

FEV1

FVC

Forced Expiratory Volume-Time Test

++R

+R

SmallAirways

IncreasingObstructiveDisease

FEV1

FVC

Normal


Respiratory Rate (breaths/min)

Wo

rk (

Kg

/min

) Normal

Restrictive

Obstructive

Disease Related Adaptations

Obstructive“slow & deep”

Restrictive“rapid & shallow”


ASMM3-receptors

b2-Receptors

Parasympathetic

ganglion in AW wall

cnssympathetic

ganglion

Vagus

ACh

Adrenal

Medulla

E

a-receptors

NEAirway

arteriole

Sympathetic

NE

E

• Bronchoconstriction

• Mucus secretion• Bronchodilation

b-agonist

drugs

Anticholinergic drugs

Airways - Neural Mechanism (In Brief)

b2-receptors


End Lecture 4

Dr HN Mayrovitz

Dr HN Mayrovitz

Lecture 59/17/19

Gas Pressures and Lung Ventilation

OBJECTIVES


• Respiratory gas values by location

• Ventilation and alveolar gas movements

• Alveolar ventilation equation application and calculation

• Alveolar gas equation and application

• Causes of uneven lung ventilation including gravity and time constants

Gas Pressures

Dr HN Mayrovitz

Dry Moist Alveolar Arterial Venous

Air Tracheal Gas Blood Blood

Air

PO2 159.6 147.2 104 100 40PCO2 0.0 0.3 40 40 46PH2O 0.0 47 47 47 47

PN2 600.4 563.5 569 573 573

P total 760 760 760 760 706

Respiratory Gas Partial Pressures

e.g. Dry Air = 0.21 x 760 torr = 159.6 Torr

Dr HN Mayrovitz1/16



Air

PO2 159.6 149.7 104 100 40PCO2 0.0 0.0 40 40 46PH2O 0.0 47 47 47 47

PN2 600.4 563.3 569 573 573

P total 760 760 760 760 706

e.g. Dry Air = 0.21 x 760 torr = 159.6 torre.g. Trachea = 0.21 x (760 - 47) = 149.7 torr

Humidification @ 37o C


Dr HN Mayrovitz2/16



Air

PO2 160 150 104 100 40PCO2 0.0 0.0 40 40 46PH2O 0.0 47 47 47 47

PN2 600 563 569 573 573

P total 760 760 760 760 706

e.g. Dry Air = 0.21 x 760 torr = 159.6 torre.g. Trachea = 0.21 x (760 - 47) = 149.7 torr

Humidification @ 37o C

ROUND-OFFS

TO BE REMEMBERED


Dr HN Mayrovitz3/16



Air

PO2 160 150 104 100 40PCO2 0.0 0.0 40 40 46PH2O 0.0 47 47 47 47

PN2 600 563 569 573 573

P total 760 760 760 760 706


Dr HN Mayrovitz4/16



Air

PO2 160 150 104 100 40PCO2 0.0 0.3 40 40 46PH2O 0.0 47 47 47 47

PN2 600 563 569 573 573

P total 760 760 760 760 706

Blood

exiting

the lung


Dr HN Mayrovitz5/16

Dry Moist Alveolar Arterial MixedAir Tracheal Gas Blood Venous

Air BloodPO2 160 150 104 100 40PCO2 0.0 0.0 40 40 46PH2O 0.0 47 47 47PN2 600 563 569 573 P total 760 760 760 760

Mixed Venous Blood = Pulmonary Artery BloodPO2 and PCO2 in dry air and trachea are “round-offs”


Dr HN Mayrovitz6/16

Ventilation


TidalVolume500 ml QT = Total (minute) Ventilation

QT = RR x TV = 6000 ml/min

RR = Respiratory Rate = 12/min

AlveolarGas Volume

AnatomicDead SpaceADS=150 ml(~1 ml/lb)


PO2 = 40SO2 = 75%PCO2= 46

SystemicVenousBlood

from RV

PO2 = 100SO2 = 97%PCO2= 40

QA=Alveolar Ventilation

QA= (TV - ADS) RR

QA= (350 X 12)

= 4200 ml/min

PO2 = 102 PCO2 = 40

PO2 = 160 → Partial Pressure (mmHg)

PCO2 = 0.3 760 x 0.21 = 159.6

Ventilation Related Processes: REVIEW

Dr HN Mayrovitz7/16

Alveolar Gas Movements

VO2VCO2

QA x FACO2

Metabolic CO2

Production

AlveolarCO2 Removed

O2 Consumed

[O2]

QA x FAO2

QA

AlveolarO2 Removed

QA x FIO2

ALVEOLARO2 Input per

Minute

BloodFrom

Pulmonary To LA

Steady State Balance for CO2 and O2

Dr HN Mayrovitz8/16

PACO2 ~ Alveolar Ventilation

CO2 Production

• Hypoventilation if ratio high: PACO2 rises

• Hyperventilation if ratio is low: PACO2 falls

Alveolar Ventilation Equation: Basic Concept

VCO2

.

QA

=K

K = 0.863 with VCO2 in ml/min and QA in L/minute.

Dr HN Mayrovitz9/16

Alveolar Ventilation (L/min)

Alv

eo

lar

P

arti

al P

ress

ure

(m

mH

g)

PACO2 =KVCO2

.

QA

PACO2=0.863 x 200 ml/min

4.2 l/min

Hyper ventilation

Hyp

ove

nti

lati

on

• Normally

Arterial PCO2

very close to

Alveolar PCO2

• PaCO2 ~ PACO2

Arterial Alveolar

• So when we talk

about alveolar

CO2 tension it

almost always

applies to arterial

Curve is for fixed CO2 production

Alveolar Ventilation Equation

40

4.2

“Blowing-off” CO2

Dr HN Mayrovitz

~41 Torr

10/16

Alveolar Gas Equation

PAO2 depends on:

Basic Concept

• Composition of inspired air (FIO2)

• Atmospheric pressure (PATM)

• Respiratory Quotient (R = CO2/O2)

• PACO2


PAO2 = (PATM - 47) x FIO2 - PACO2 [FIO2 + (1-FIO2)/ R]

R = respiratory exchange ratio= CO2 produced/O2 consumed

PAO2 = (760-47) x .21 - 40 [.21 + (1-.21)/.8]

PAO2 = (713) x .21 - 40 [1.2]

PAO2 ~ = 150 - 40 [1.2] = 102 torr

PAO2 ~ 150 - 1.2 PACO2 for room air at sea level

Alveolar Gas Equation


Uneven Alveolar Ventilation

Gravity Main Effects

• Alveoli at base have less volumebut greater compliance

• Result is a better ventilation ofbase alveoli during normal TV


PTL = PALV - PPL

Gravity Effects

PALV

Does not

depend

on

gravity

BUT

PPLdoes!

So ….

PTLvaries

with

height

1. Lung tissue behavesas a low density fluidr= 0.28 g/cm2

2. Intrapleural fluid heightrepresents a “column”

Higher intrapleural pressure (PPL)

•Less Transmural Pressure•Less Alveolar Volume• Less PREC → Greater C

BASE

Dr HN Mayrovitz

Uneven Ventilation – Variable Time Constants

Time Constant Effects

• Time Constant = R x C = t

• Time to fill/empty ~ t

• Variability in t causes uneven

alveolar ventilation within lung


Fills Slower

80% at 2 sec

(Normal)

Take inspiration time = 2 seconds

Uneven Ventilation due to

variability in Time Constants

B&L 27.3

Vo

lum

e C

ha

ng

e (

% o

f fi

na

l vo

lum

e)

Seconds

R

C Fills Faster but

only half as much

Effects of Uneven Time Constants

A source of non-gravity related uneven ventilation


End Lecture 5

Dr HN Mayrovitz

Lecture 69/20/19

Gas Diffusion and Transport

Dr HN Mayrovitz

OBJECTIVES


• Blood oxygen content equation application and calculation

• Oxygen delivered – carbon dioxide removed circuit with calculations

• Lung diffusion capacity and factors affecting its value

• Oxygen loading and unloading dynamics

• Carbon dioxide loading and unloading dynamics

• Oxygen deficiency terms and sources

0

510

1520

25

3035

40

4550

5560

65

7075

80

8590

95100

105

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105

PO2 (mmHg)

SO2

(%)

Blood Oxygen Content EquationSO

2(%

)

PO2 (mmHg)

23, 400

PO2 [ PO22 + 150]

+ 1

1SAT =

Severinghaus Equation

venous

Arterial blood20 ml O2/dl

D = 5 mlO2/dl

pH = 7.40T = 37oC

Dr HN Mayrovitz

97.4%

[O2] = 1.34 [Hb] (%Sat/100) + 0.003PO2

ml/dl wb

g/dl whole blood (wb)(34 g/dl rbc x Hct)34 x 0.44 = 15 gHb/dl wb

Amountdissolved

[O2] = 1.34 x 15 x 0.974 = 19.6 mlO2/dl + 0.27

Hb4O2

O2

O2

O2

1/11

LUNG

LA

LV

RA

RV

SYSTEMIC

AIR

O2

CO2

300 ml O2/dl/min

“Average” O2 needed

240 ml CO2/dl/min

“Average”CO2 generated

Air in – and –Air out →O2 delivered and CO2 removed

For every ml of O2 used 0.8 ml CO2 produced

5 mlO2/dl bloodmust be supplied

4 mlCO2/dl bloodmust be removed

CO = 6 L/min = 60 (dl units/min)

Dr HN Mayrovitz

Respiratory QuotientCO2 produced/O2 consumed

Lipid → 0.70Protein → 0.80Carbohydrate → 1.0Average →0.80

Each dl unitmust get5 mlO2

2/11

O2

A

d

PAO2PaO2

P1P2

DP

AlveolusCapillary

f

f = D (A/d) DP

1. Area (A)2. Thickness (d)3. Pressure Difference (DP)4. Diffusion coefficient (D)

Lung“Membrane”

Main Factors

Here “a” refers to blood exitingpulmonary capillaries.

A.M

em

bra

ne

Inte

rsti

tial

Pla

sma

RB

C

C.M

em

bra

ne

A

fO2

Basic Diffusion Processes

Dr HN Mayrovitz 3/11

Lung Diffusing Capacity

DL takes into account all factors that effect whole lung diffusion

DL = ml O2/min from alveoli to blood

(alveolar) PAO2 - PaO2 (capillary)

Alveolar Gas

PAO2

Capillary PaO2

fO2DL is a form of “conductance”

i.e. flow/DP

DL=

fO2

PA O2 - PaO2

Dr HN Mayrovitz4/11

O2

Factors Decreasing DL

Diffusion Distance

•Alveolar Wall Thickening

•Alveoli-Capillary separation by:

edema, exudate or fibrous tissue

Surface Area

•Fewer functioning capillaries

•Fewer functioning alveoli

•Disrupt normal alveolar architecture

Red Blood Cells and Diffusion Resistance

•Decreased rbc membrane permeability

•Decreased Hb O2 affinity

•Decreased total amount of Hb available

Dr HN Mayrovitz5/11

Gas dynamics

Loading up with O2 in Lung

Alveoli

Lung Capillaries

Hb

PAO2

Air

Airways

PCO2 RBC “carrier that is carried”

100

80

60

40

20

0

0 20 40 60 80 100

SO2

(%)ml O2

100 mlblood

0

20Arterial Blood

Venous15

Loading O2 in Lung

Blood PO2 (mmHg)

97%

75%

PCO2 = a [O2]

40 80 100 100 100 100 PCO2

100 mmHg

Equilibrates at ~ 1/3 capillary length

HbHb

a = 1/KO2


Unloading O2 to Tissues

40 40 40 40 80 100 PCO2

Equilibrates at ~ 1/3 capillary length

HbHb

Tissue Fluid PTO2

Cell using O2

PCELLO2

40 40 40 40 40 40

5-25

100

80

60

40

20

0

0 20 40 60 80 100

SO2

(%)ml O2

100 mlblood

0

20Arterial Blood

Venous15

Loading O2 in Lung

Blood PO2 (mmHg)

97%

75%


Picking Up CO2 from Tissues

46 46 46 44 42 40 PCCO2HbHb

Tissue Fluid PTCO2

Cell producing CO2

PCELLCO2

CO2 + H20 → H2CO3

Carbonic Acid 5%

Carbamino Compounds 5%

HCO3- 90%

Bicarbonate dissolved

[CO2]ml/100 ml

PCO2 (mmHg)

PCCO2END of

Lung Capillary

52

40 46

SO2 = 97%

SO2 = 75%

PCCO2START of

Lung Capillary

50

48

Systemic Capillary

To Lung

From Lung


0 0.15 0.30 0.45 0.60 0.75

Time RBC in Capillary (sec)or Distance Traversed (mm)

100

90

80

70

60

50

40

Blo

od

PO

2

(To

rr)

Enters Leaves

Normal Diffusion

ModerateImpairment

SevereImpairment

PAO2=102

Exercise - capillary transit time reduced

PvO2 = 40 PaO2 =?

Capillary Blood Oxygenation

100

90

80

70

60

50

40

~1 mm/sec


CO2 vs. O2 Curves

0 10 20 30 40 50 60 70 80

O2 or CO2 Pressure (Torr)

BloodO2 or CO2

Content(ml/100 ml)

70

60

50

40

30

20

10

0

CO2

O2Near-Flat

If REDUCED VENTILATIONAlveolar PCO2 risesBlood PCO2 directlyfollows

If REDUCED VENTILATIONAlveolar PO2 falls but

PO2 change is “buffered”

O2

CO2


Oxygen Deficiency Terms and Sources

ANOXIA = No O2

HYPOXIA = Inadequate O2 Available for Tissue NeedsHYPOXEMIA = Hypoxic Hypoxia = Low PaO2

•

HEMATOLOGICAL HYPOXIALow Hb to bind/carry O2 but normal PO2 → Anemia, Carbon Monoxide Poisoning

ISCHEMIC HYPOXIA (Hypoperfusion Hypoxia or Stagnant Hypoxia)Low tissue O2 due to low systemic blood flow to the area (blood PO2 is normal)

HISTOXIC HYPOXIANormal O2 supplied (Normal PaO2 and blood flow) but O2 can’t be utilized bytissue → Cyanide Poisoning (Blocks oxidative phosphorylation)

Ventilation/Perfusion 15/20

Low FIO2 → Low O2 in inspired air → Fire

Low PATM → Altitude

Low QA → +Air way resistance, CNS depression, neural or muscular deficits

Low V/Q → increased number of low ventilation or high blood perfusion areas

Low DL → Edema, Fibrosis

R-L Shunt → Anatomical → Blood bypasses alveoli


End Lecture 6

Lecture 7 9/20/19Ventilation –Perfusion Matching

Dr HN Mayrovitz

OBJECTIVES


• Ventilation-perfusion (V/Q) matching concept

• Evaluate sources and effects of altered (V/Q) on blood gasses

• Hypoxic pulmonary vasoconstriction (HPV)

• Pulmonary shunting types and effects on blood gasses

• A – a gradient: Concept and application

Ventilation-Perfusion Matching

Basic ConceptIt is neither ventilation nor perfusionalone that determines arterial bloodgases. It is the ratio of ventilationto perfusion that is the determinant!

Ventilation/Perfusion = V/Q ratio

Dr HN Mayrovitz1/15

A. Ventilation-Perfusion Concept

PO2 = 40

SO2 = 75%

PCO2= 46

Systemic

Venous

Blood

from RVPO2 = 100

SO2 = 97%

PCO2= 40

QA = Alveolar Ventilation

= 4200 ml/min

250 ml O2/min

5000 ml/min

Assume that an alveolar ventilation of 4200 ml/min

will deliver 250 ml O2/min to capillary blood.

Each 100 ml blood unit picks up 5 ml of O2

If blood flow is 5000 ml/min then each of the (50) 100 ml of blood must pick up 5 ml of O2. This results in a proper

“arterialization” of blood exiting the lung.

5000 ml =50 ‘100 ml blood’ units

250mlO2/50units = 5 mlO2/unit

V/Q 4200/5000

0.84

Ventilation/Perfusion Dr HN Mayrovitz

PO2 = 40

SO2 = 75%

PCO2= 46

Systemic

Venous

Blood

from RV


= 4200 ml/min

250 ml O2/min

10,000 ml/min

Now suppose ventilation stays constant but blood flow increases to 10,000 ml/min.

Each 100 ml blood unit picks up 2.5 ml of O2

100 “100 ml blood” units

250mlO2/100units

= 2.5 mlO2/unit

Now, 100 “100 ml units” pass each minute. Soooo….. each will pick up only 2.5 ml of O2 since QA is constant. Since this is 1/2 as much as needed to properly saturate the blood, Sooo …….. PaO2 will fall!

PaO2

B. Ventilation-Perfusion Concept

V/Q 4200/10000

0.42

Dr HN Mayrovitz

PO2 = 40

SO2 = 75%

PCO2= 46

Systemic

Venous

Blood

from RVPO2 = 100

SO2 = 97%

PCO2= 40


= 2100 ml/min

125 ml O2/min

2500 ml/min

Now suppose ventilation and perfusion become 1/2 of

what they originally were. Now each 100 ml of blood

again picks up 5.0 ml of O2. Thus Ventilation is again

optimally matched to perfusion to properly cause the

needed blood O2 saturation.

Each 100 ml blood unit picks up 5.0 ml of O2

C. Ventilation-Perfusion Concept

25 “100 ml blood” units

125mlO2/25units

= 5.0 mlO2/unit

V/Q 4200/5000

0.84

Dr HN Mayrovitz

Number of lung units with low V/Q

Pa C

O2

Pa O

2

PaO2

PaCO2

0

Another View of Mismatching

Dr HN Mayrovitz5/15

PaCO2 PaO2

(V/Q)0.4 0.84 1.2 1.6

00

4

0

42

44

50

10

0

1

50

CO2

O2

Hypoxemia

Hypocapnia

Respiratory

Alkalosis

Respiratory

Acidosis

Effects of Changes in V/Q

IncreaseDecrease

Hyperoxemia

Hypercapnia

Dr HN Mayrovitz6/15

0

1 2

3

TopBottom

Qor

V

V/Q

V

Q

V/Q

Regional V/Q Variations

PCO2 42T

PCO2 28T

PO2 90T

PO2 130T

Matched

>match

V/Q<match

V/Q

Position Vertically in Lung

0.84

Dr HN Mayrovitz7/15

V/Q

PaCO2 PaO2

(V/Q)0.4 0.84 1.2 1.6

00

4

0

42

4

4

50

1

00

15

0

CO2

O2

Hypoxemia

Hypocapnia

Respiratory

Alkalosis

Respiratory

Acidosis

Hyperoxemia

Hypercapnia

V/Q

Good Arterialized

PO2

MixedVenousBlood

(PulmonaryArtery Flow)

Perfectly Matched

Clinical Correlation: Ventilation matched to Perfusion


PaCO2 PaO2

(V/Q)0.4 0.84 1.2 1.6

00

4

0

42

4

4

50

1

00

150

CO2

O2

Hypoxemia

Hypocapnia

Respiratory

Alkalosis

Respiratory

Acidosis

Hyperoxemia

Hypercapnia

MixedVenousBlood


PulmonaryEmbolism

V/Q

LOWPaO2

Clinical Correlation: Pulmonary Embolism

Low V/Q


V/Q V/Q

MixedVenousBlood


High V/Q

Clinical Correlation: Hyperventilation

PaCO2 PaO2

(V/Q)0.4 0.84 1.2 1.6

00

4

0

4

2

4

4

50

1

00

1

50

CO2

O2

Hypoxemia

Hypocapnia

Respiratory

Alkalosis

Respiratory

Acidosis

IncreaseDecrease

Hyperoxemia

Hypercapnia

LOWPaCO2


100

80

60

40

20

0

BloodFlow(% )

Alveolar PO20 50 100 150 200 250 300 350

Hypoxic Pulmonary Vasoconstriction (HPV)

Effect of reducing ALVEOLAR PO2 on Local Blood Flow

~70 mmHg

Flow reduction Produces Better V/Q match

Poorly

oxygenated

blood

Vasconstriction

shunts blood to

better oxygenated

alveoli

AW

PO2

100 60

Shunts

Anatomical Shunts: systemic venous blood• Bronchial veins• Thebesian veins• Pleural veins

Intrapulmonary Shunts: • Mixed venous blood has

zero alveolar gas exchange (e.g. airway obstruction)

• Low V/Q → low O2 mixes with all oxygenated blood

Blood fromLow V/Q units

Blood fromAlveolar DS

INTRAPULMONARY SHUNTS

Bronchial V.Anatomical

Shunt

LUNG

PHYSIOLOGICAL SHUNT Anatomical Shunt + Intrapulmonary Shunt

Mixing of low oxygenated blood with arterial blood


Normal: Minimal Shunting

PO2=40PCO2=46

PO2=104PCO2=40

PO2=104PCO2=40

PO2=100PCO2=40

PulmonaryArtery

AnatomicDead Space

PIO2=150PCO2=0Alveoli

Normal

A – a Gradient

Rule of thumb: Normal gradient should be ≤ (Age/4) + 4

60 year old might have a gradient of (60/4) + 4 = 19 TorrDr HN Mayrovitz12/15

• 100% O2 will not abolish hypoxemia• Shunted blood never exposed to O2

• Non-shunted blood already near max saturation

Anatomical shunt: Features

PO2=40PCO2=46

PO2=104PCO2=40

PO2=104PCO2=40

PO2=60PCO2=39

PulmonaryArtery

AnatomicDead Space

PIO2=150PCO2=0Alveoli

Normal

PO2=40PCO2=46

PulmonaryVeinO2

“diluted”

ShuntRight-to-Left


Ventilation Deficit• e.g. mucous obstruction - airway edema - bronchospasm• foreign body - tumor - etc

100% O2 WILL improve situation

Low V’

Blood

Flow

PA PV

Intrapulmonary Shunt

Low V/Q

Low PO2

High PCO2


A-a Gradient Question to Ponder

PAO2=102 PaO2=94

Right Heart Left Heart

Thebesian Veins

Bronchial V. Aorta

Dr HN Mayrovitz

Bill is 24 years old. A) What is his A-a gradient and B) is it within the normal range for his age?

15/15

End Lecture 7

Dr HN Mayrovitz

Lecture 8 10/2/19Respiratory System

Controls and Reflexes

Dr HN Mayrovitz

OBJECTIVES


• Overall respiratory control defining feed back variables and mechanisms

• Medullary and Pontine respiratory groups and their actions

• Normal vs. abnormal breathing patterns

• Respiratory mechanical receptors: types and actions

• Herring-Breuer reflexes

• Peripheral (PCR) and Central (CCR) Chemoreceptors: types and actions

• Ventilation changes due to O2 changes, CO2 changes and high altitude

Impulses to

Respiratory

Muscles

Ventilation control

Via changes in

RR and TV

Peripheral and Central

Chemo and Mechanical

Receptor Feedback

Other Inputs

Basic Respiratory Control Overview

Inspire Exp Inspire

Central Pattern Generator

Pons

VR

G

VR

G

DR

G

DR

G

PRG

Brain stem

Respiratory

Center

Respiratory

Center


Spinal Respiratory

Motorneurons

Respiratory Muscles

Ventilation: TV/RR

Blood Gases

Skeletal

Muscle

Receptors

Receptors: lung & airways

chest wall & diaphragm

Peripheral Chemoreceptors

Central ChemoreceptorsCSF [H+]

Emotions

(Forebrain)LimbicReticular

Formation

Sensory (pain, startle, etc)

Upper

Airway

Muscles

pharynx

larynx

flare nostrils

open mouth

Airway

Smooth

Muscle

Pons

VR

G

VR

G

DR

G

DR

G

PRG

Brain stem

Respiratory

Center

Phrenic (diaphragm)

Spinal n. (intercostals, abd)

CPG

Neocortex

(Voluntary)

+CO2, -pH

-O2, +CO2, -pH


Impulses

Inspiration Expiration Inspiration

Impulses to Respiratory Muscles From MedullaryCentral Pattern Generator (CPG) Cause Inspiration

Impulses

per sec

Lung

Volume

TV

1/RR


Spinal Cord

Med

ull

a

C1

1st cervical

Nerve

X

IX

Pons

4th Ventricle

VRG

DRG

Ventral

Respiratory

Group

PRG

ApneusticCenter

Respiratory Cell Groups

phrenic

Receptorfeedback

Dorsal

Respiratory

Group

Pontine Respiratory Group(Pneumotaxic Center)

4/21Dr HN Mayrovitz

E

E

IN

Internal intercostalabdominal muscles

ININ

Diaphragmand external intercostals

INDiaphragm

and external intercostals& accessory

UpperAirwaysLarynxpharynxtongue

VRG DRG

Medullary Respiratory Center

Pre-Botzingercomplexpossible

pacemakerregion

IN = InspiratoryE = Expiratory

DRG

E

VRG

E


Pons

PRG

Pneumotaxic Center

• In upper pons

• Some neurons active during

inspiration & some in expiration

• Important role in switching

off/limiting inspiration

• If damaged leads to apneusis:

prolonged inspiratory spasms

with short intervals of expiration

• Also fine-tunes breathing based

on receptor feedback

Pontine Respiratory Group (PRG)


Pneumotaxic Center (PRG)

Apneustic Center

Inspiratory

Center

DRG

Expiratory

Center

VRG

Maintenance of signal

Prolongs inspiration

Inhibits apneustic output

Switches off Inspiration

NTS

To inspiratory m.

Impulses/s

Receptor

Feedback

Via IX & X

Basic rhythm is generated in medulla

(Central Pattern Generator)

CPG → Cause is unknown

Respiratory Center Actions: Summary

Pons

Medulla

Pons

VR

G

VR

G

DR

G

DR

G

PRG

Brain stem

Respiratory

Center

CPG

NTS = Nucleus Tractus Solatarius


Normal

Apneustic

Pneumotaxic Center (PRG)

Apneustic Center

Inspiratory

Center

DRG

Expiratory

Center

VRG

Maintenance of signal

Prolongs inspiration

Inhibits apneustic output

Switches off Inspiration

NTS

To inspiratory m.

Impulses/s

Receptor

Feedback

Via IX & X

Inhibitionlost

Cheynes-Stokes

Over-correction

Abnormal Breathing Patterns

Tidal VolumeCrescendo

Apnea


C-Fiber

Endings

Slowly

Adapting

Receptors

Rapidly

Adapting

Receptors

Nasal

Pharyngial

Epipharyngeal

Laryngial

Respiratory MechanoreceptorsReceptors Located in

• Upper respiratory

• Tracheo-bronchial tree

• Lung parenchyma

Broadly three types

• Slowly Adapting (SAR)

Among ASM cells

• Rapidly Adapting (RAR)

Among airway epithelial cells

• C-fiber endings (J-receptors)

near blood vessels/capillaries

Vagal Afferents

• Connect to respiratory cntr

• Initiate many reflexes


Bronchoconstriction:

• Prevents deeper penetration into airway

• Produces higher velocity airstream during sneeze or cough

Sneeze: Stimulation of nose or nasopharynx receptors

Afferent pathways via trigeminal and olfactory nerves

Cough: Stimulation of tracheobronchial receptors

Afferent pathways via vagus nerves

Mechanical/Chemical Irritant Reflexes (RAR)

Receptors in nasal mucosa, upper airways, tracheobronchial tree

and possibly alveoli trigger bronchoconstriction and sneeze or cough

Cough/Sneeze Process:

•Deep inspiration is followed by forced expiration with closed glottis

•Intrapleural pressure rises precipitously ~ 100 mmHg

•Glottis opens and high velocity exhalation air stream results

Sneeze: Through nose Cough: Through mouth10/21 Dr HN Mayrovitz

Hering-Breuer INFLATION Reflex

DRG

VRG

Ia

Inspiratory m.

Impulses to inspiratory muscles

are decreased

•Reduces inspiration duration

•Reduces TV •Prevents overdistention

SAR among ASM cells

Ia

Ib

H-B Inflation Reflex Operative in •Adults if TV > 800 ml• Infants

Too much lung Inflation

Inhibitory impulses to DRG via Vagus

a

DRG

VRG

Ib

Hyperpnea•Tachypnea +RR•Hyperpnea +TV & +RR

Ia

Ib

• Pneumothorax → RAR• Trigger for sighs• Maintain Infant FRC

low chest wall force

Less stretch receptor activitycauses a reflex that promotes either/bothincreased TV and RR

Impulses to inspiratory muscles

are increased

Hering-Breuer DEFLATION Reflex

b

12/21Dr HN Mayrovitz

H+

HCO3-

CO2

chemoreceptor

CSFSkull

Capillary

Central Chemoreceptors (CCR)

Blood-BrainBarrier

H+

VentilationControl


• CCR in brain parenchyma bathed in brain extracellular fluid/CSF

• If blood gases and pH near normal CCR are main control of ventilation

• CCR are sensitive to arterial hypercapnia (and associated fall in pH)

• CCR actually sense pH (H+) around receptor neurons bathed in CSF

• pH changes may occur due to:

1) increased cerebral blood CO2 diffusing across the blood brain

barrier resulting in a rapid (60 sec) decrease in the pH of CSF

2) decreased pH of brain or CSF not due to changes in PaCO2 (delayed)

• CCR do not respond to hypoxia

• CCR and PCR both affect ventilation response to increased CO2 levels

Dependence of Ventilation

on pH of CSF

pH of CSF

Ve

nti

lati

on

(L

/min

)

7.15 7.20 7.25 7.30 7.35

Normal

REVIEW: Central Chemoreceptors (CCR)

H+

HCO3-

CO2

chemoreceptor

CSFSkull

Capillary

Blood-BrainBarrier

H+

VentilationControl

Vas

odila

tion


Peripheral Chemoreceptors (PCR)

• Located bilaterally in carotid and aortic bodies

• Respond to Hypoxia, Hypercapnia and Acidosis

• Afferent pathways for:

Carotid body → Hering’s nerve

Aortic body → vagus nerve

• Large afferent impulse traffic at normal blood gases

• Increased afferent activity caused by

(1) decreased arterial PaO2

(2) increased PaCO2

(3) decreased arterial pH

• Feedback to respiratory center → increased V’

• Response to hypoxemia depends on PaCO2 & pH

More PaCO2 or lower pH → greater DV’ for same DPaO2

NTS IN

DRG

Sympathetic N. Arteriole

FenestratedCapillaries

GlomusCell

-PO2

+PCO2

-pH

MedullaOblongata

Respiration•RATE•TIDAL VOLUME

Afferent Response to changes in PaO2

Note large rate of increase

below about 60-70 torr

PaO2 of blood perfusing

carotid body is varied

PaCO2 and pH normal

0 50 100 200

Imp

uls

es

/se

cPaO2 (mmHg)


Ventilation Response to changes

in PaO2depends on level of PaCO2

20 40 60 80 100 120

PaO2 (mmHg)

Ven

tila

tio

n (

L/m

in)

PaCO2 = 40 mmHg

PaCO2 = 50 mmHg

Slope of lines define the

sensitivity of the response

to changes in PaO2

Normal

PaCO2 Effect on Response to Changes in PaO2




20 40 60 80 100 120

PaO2 (mmHg)

Ven

tila

tio

n (

L/m

in)

PaCO2 = 40 mmHg

PaCO2 = 50 mmHg



to changes in PaO2

+V’ due to

+ PaCO2

Normal

PaCO2 Effect on Response to Changes in PaO2




20 40 60 80 100 120

PaO2 (mmHg)

Ven

tila

tio

n (

L/m

in)

PaCO2 = 40 mmHg

PaCO2 = 50 mmHg



to changes in PaO2

• Ventilation response to hypoxia depends on level of PaCO2

• +PaCO2 and -pH cause more DVent (DV’) for same D in PaO2

dV’/dPaO2

+V’ due to

+ PaCO2

Normal

PaCO2 Affects Response to Changes in PaO2


Ventilation Response to CO2

Carotid Body Perfusion-High CO2

Rapid

Ventilation

increase

TV & RATE

INCREASE

CO2

Hyperpnea19/21 Dr HN Mayrovitz

REVIEW: Ventilation Responses to CO2

• Breath rate & depth regulated to maintain PaCO2 close to 40 mmHg• Ventilation increases nearly linearly with PaCO2 AT FIXED PaO2

• Change in ventilation for equal changes in PaCO2 depends on PaO2

Lower PaO2 → greater change in ventilation (k is greater)So HYPOXEMIA increases sensitivity of the CO2 ventilatory response

sensitivity = dV’/dPaCO2 = k = f (PaO2)• At any PaCO2 level → a pH decrease causes greater impulse response

30 35 40 45 50 55

PaCO2 (mmHg)

Imp

uls

e/s

ec

pH=7.25

pH=7.45

Carotid Body AfferentVentilation Response to changes in PaCO2

30 35 40 45 50 55

PaCO2 (mmHg)

Ve

nti

lati

on

(L

/min

)

PaO2=40

PaO2=60

PaO2=100

Actions of

both CCR

and PCR

V = k PaCO2

k=f(PaO2)


High Altitude: Respiratory Adaptation

Decreased Atmospheric Pressure ~ Hypoxemia

Peripheral Chemoreceptors drive increased ventilation• Increases PaO2 but Decreases PaCO2

• Decreased CO2 effects Central Chemoreceptors (+pH) • Initially counter to hypoxia induced hyperpnea• CSF and arterial pH tend to normalize over days • Renal excretion of HCO3-

• Early acute Mountain Sickness possiblePolycythemia - Increases O2 carrying capacity

P50 Shift to Right - Better O2 unloading

Increased Capillary Density


End Lecture 8

Dr HN Mayrovitz

Documents

Respiratory Physiologyclinsoft.org/drmayrovitz/PHYSIOLOGY/RESPIRATION/COM...2 x P ATM = 0.21 x 760 = 159.6 →160 mmHg Q T = Volume/breath x Respiratory Rate Q T = Tidal volume x RR