pulmonary pathophysiology

7/17/2019 Pulmonary Pathophysiology

http://slidepdf.com/reader/full/pulmonary-pathophysiology-568c25a9a550f 1/146

The CF Foundation’s Mission

Thomas G. Keens, M.D.Professor of Pediatrics, Physiology and Biophysics,

Keck School of Medicine of the University of Sothern !alifornia.

Division of Pediatric Plmonology and Sleep Medicine,

!hildren"s #ospital $os %ngeles.

&'mail(

)o !onflicts of *nterest to Disclose

Mechanisms of

Plmonary Disease

)+-B( %dvanced Pathophysiology.

%dvanced )rse Practice Program.

U!$% School of )rsing. cto/er +0, +-01.



2espiratory

Physiology and

Pathophysiology






The maintenance

of normal arterial

o3ygen tension4Po+5, car/on

dio3ide tension

4Pco+5, and p#,6ithot e3cessive

cardiac or

plmonary 6ork.

)ormal $ng7nction



• %de8ate

9entilation.

• %de8ate

Perfsion.

• Distri/tion of

9entilation.

• Diffsion of + and!+ across the

alveolar'capillary

mem/rane.!omroe, :.#., et al. The Lung. ;ear BookMedical P/lishers, !hicago, 0<=+.

%de8ate Gas &3change



!omroe, :.#., et al. The Lung. ;ear BookMedical P/lishers, !hicago, 0<=+.

•)on'niform

distri/tion of

ventilation is

the mostimportant

case of gas

e3changea/normalities

in hman lng

disease.

%de8ate Gas &3change



)etter, 7.#. Respiratory System. 9olme >, !*B%!ollection of Medical *llstrations. 0<><.

•%ir6ays(

•+ generations.

•-'0=( condcting

air6ays.•0>'+( respiratory

/ronchioles.

•%lveoli(

•--'1-- million

alveoli.

•Gas e3change

srface.

Strctre ofthe $ngs


http://slidepdf.com/reader/full/pulmonary-pathophysiology-568c25a9a550f 9/146Berne, 2.M., and M.). $evy. Principles of Physiology. Mos/y, St. $ois, +---.



• Site of most gas e3change.

• %dlts have --'1-- million

alveoli.• + and !+ e3change is /y

diffsion across the alveolar

capillary mem/rane.

• Thin mem/rane -.1'0.- m thick.

%lveoli


http://slidepdf.com/reader/full/pulmonary-pathophysiology-568c25a9a550f 12/146Berne, 2.M., and M.). $ev . Princi les of Ph siolo . Mos/ , St. $ois, +---.


http://slidepdf.com/reader/full/pulmonary-pathophysiology-568c25a9a550f 13/146Tisi, G.M. Pulmonary Physiology in Clinical Medicine. ?illiams and ?ilkins, Baltimore, 0<@-.



%lveolar srface area of adlt lngs A >1 M+ A <- s8are

yards. 40.> C0=-thE the area of a college foot/all field5.

L

A

%lveolar Srface %rea

of %dlt $ngs



!omroe, :.#., et al. The Lung. ;ear Book Medical P/lishers, !hicago, 0<=+.



!ompensation for

2egional #ypo3ia

• ne can not correct regional

↓

Po+ /y↑

9F in another

lng region.

•Ths,↓

Po+ is the most

sensitive inde3 of the

presence of lng disease.

• ne can ↑Po+ /y ↑+

entering the hypo3ic region,

/y↑

7*o+.



Tisi, G.M. Pulmonary Physiology in Clinical Medicine. ?illiams and ?ilkins, Baltimore, 0<@-.



Types of Respiratory Dead Space


Types of 2espiratory Dead Space

!ondcting %lveoli 6ith

%ir6ays )o Bloodflo6



•Diffsion defect.

•#ypoventilation.

•Decreased 9F.

•2ight'to'$eft shnt.

!ases of #ypo3emia



•#ypoventilation.

•Decreased 9F.

!ases of #ypercapnia



%ir6ay/strction

Decreased!ompliance

Distri/tion of 9entilation



•!ompliance.

•2esistance.

!ompliance A

9olme

Pressre

2esistance A

Pressre

7lo6

Plmonary Mechanics



•Slope of the line is

compliance.

•The pressre'

volme crve of the

lng is not a line,

/t a loop.

•2eferred to as

hysteresis.Tisi, G.M. Pulmonary Physiology in Clinical Medicine.?illiams and ?ilkins, Baltimore, 0<@-.

Plmonary

!ompliance 4!$5

!$ A 9olme

Pressre




!$ = 9olme

Pressre




2esistance A Pressre

7lo6



&3trathoracic Upper %ir6ay /strction



*ntra Plmonary %ir6ay /strction



P % ti



Sasaki, #., et al. J. Appl. Physiol., 4! @1@'@=<, 0<>@.

Pressre %cting

on %ir6ays

%i / t ti



%ir6ay /strction

!herniack, 2.M., et al. Respiration in "ealth and #isease. ?.B. Sanders, Philadelphia, 0<>+.

# i fl ti



#yperinflation


%t l t i



%telectasis


%i / t ti



• *ncreased air6ay resistance.• Bronchospasm.

• %ir6ay *nflammation.

• Mcos plgging.

• &3trinsic compression of the air6ay.

• 7oreign /ody in the air6ay.

• Decreased &lastic 2ecoil.

• &mphysema.

%ir6ay /strction

%i * fl ti



!ases air6ayo/strction /y(

•Mcosal edema.

• Mcos plgging.

•*ncreased mcos

secretions.

• Bronchospasm.

!ommon in(

• %sthma.

• !hronic

/ronchitis.

• !ystic

7i/rosis.

%ir6ay *nflammation

%i / t ti




%ir6ay /strction

& h




&mphysema



)etter, 7.#. Respiratory System. 9olme >, !*B% !ollection of Medical *llstrations. 0<><.

$ng



2est &3ercise

$ng

Base

$ng

%pe3



)+-B( %dvanced Pathophysiology






PlmonaryDisorders

P l Di d



Plmonary Disorders

•Pnemonia.

•%spiration

pnemonia.

• *nflena pnemonia.

• T/erclosis.

•Plmonary fi/rosis.

•Bronchiolitis.

•%sthma.

•!hronic /ronchitis.

•&mphysema.

•Bronchiectasis.

•!ystic fi/rosis.

•Pnemothora3.

•Plmonary edema.

•Plmonaryem/ols.

P i



• *nfection of the lng.• %lveoli are filled 6ith

infected material.

• 2e8ires treatment

of the infection 6ith

anti/iotics.

• Systemic

anti/iotics are

sally re8ired.

Pnemonia

Pne monia



• *nfection may alsocase(

• Bronchospasm

re8iring/ronchodilators.

• ↑ plmonary

capillarypermea/ility

casing edema.

Pnemonia



)ormal !hest H'ray



Pnemonia



Pnemonia

2adiographic Patterns



2$$

2U$

2M$

$U$

$$$

2adiographic Patterns

of $o/ar *nfiltrates

Pnemonia !aveats



•2ecrrent pnemonias are not normal.

•!onsider nderlying disorders 6hich might

predispose the patient to I+ pnemonias(

• !hronic $ng Disease.

• 2ecrrent aspiration.

• Untreated asthma.

• !ystic 7i/rosis.• %/normal mcociliary clearance, host

defenses, or immne deficiency,

• !ongenital malformations.

Pnemonia !aveats

%spiration



• %spiration occrs

most commonly in

patients 6ith

s6allo6ingdysfnction.

• &lderly.

•)erologicallyimpaired.

• Seires.

• G&2D.

%spiration

Pnemonia

%spiration Pnemonia



2M$ is the most common site.

%spiration Pnemonia



0<0@ *nflena pandemic killed as

many as 1-,---,--- people 6orld'



*nflena 9irs



*nflena Pnemonia

*nflena



• %nnal ot/reaksin 6inter.

• #igh fever, mscle

aches.

• Pnemonia is the

sal case of

death.• %ntiviral agents

only partly

effective.

*nflena

Pnemonia



T/erclosis



• +,---,--- deaths per

year 6orld6ide.

• ne'third of 6orld"s

poplation infected.

• I@,---,--- ne6cases diagnosed

each year.

• Mltiple drg

resistant TB

emerging as a

6orld6ide p/lic

health threat.

T/erclosis



T/erclosis 4Gohn comple35



4 5

T/erclosis 4Gohn comple35



T/erclosis



Miliary T/erclosis

T/erclosis( !aseating Granloma



T/erclosis( !aseating Granloma



T/erclosis !avitary $ng Disease



T/erclin Skin Test

T/erclin Skin Test



• Diagnoses TB infection.

•Positive +'0+ 6eeks afterinfection.

• !riteria for positive TST.

*ndration Poplation 42isk5

1 mm*mmnocompromised

!ontact 6ith TBpatient.

0- mm2isk of dissemination.*ncreased e3posre to

TB disease.

01 mm )o risk factors.%merican %cademy of Pediatrics.

The Red $oo%. +--=.

T/erclin Skin Test



• Diagnoses TB infection.

•Positive +'0+ 6eeks afterinfection.

• !riteria for positive TST.

*ndration Poplation 42isk5

1 mm*mmnocompromised

!ontact 6ith TBpatient.

0- mm2isk of dissemination.*ncreased e3posre to

TB disease.

01 mm )o risk factors.%merican %cademy of Pediatrics.

The Red $oo%. +--=.



*nterstitial Pnemonitis



•*f ntreated, interstitial

pnemonitis progresses to

fi/rosis, destroying alveolar

tisse and /lood vessels ↓

lng volmes and↓

!$.

•Patients have shortness of

/reath, tachypnea, and↓

e3ercise tolerance.

•May reslt from many types

of lng inJry.

and 7i/rosis



Digital !l//ing



!ommonly seen in chronic lng diseases

associated 6ith hypo3ia andor inflammation.

Digital !l//ing



Plmonary 7i/rosis



)ormal !hest !T Scan



Plmonary 7i/rosis



Plmonary 7i/rosis

*nterstitial Pnemonitis



• 2estrictive lng disease.• Treatment is that of the

nderlying case.

• #igh dose systemiccorticosteroids sppress

active inflammation.

• ther chronic medications(

• %athioprine.

• !yclophosphamide.

•#ydro3ychlora8ine.

and 7i/rosis

Bronchiolitis



•%cte, life'threatening

disorder in infants.

•*nfectios

inflammation of

/ronchioles >1'-- indiameter.

•2espiratory syncytial

virs 42S95.•#ypo3ia, air6ay

o/strction, and

hyperinflation.

o c o t s



Bronchiolitis

%sthma



• Most common chronic lng

disease.

• 01 of U.S. children.

•!haracteried /y episodes of

air6ay narro6ing reslting from

/ronchospasm and

inflammation.

• *nhalation is the rote of choicefor the administration of

medications, as it is associated

6ith the least side effects.

%sthma



&3pert Panel 2eport ( &uidelines for the #iagnosis and Management of Asthma, +-->.

*nflammation



•%ir6ay mcosal inflammation

cases s6elling of the air6ay

lining and mcos secretion.

• 2elease of inflammatorymediators.

• !ytokines.

• $ekotrienes.

• Primary target to control asthma

symptoms.

*nflammation

)e/liers



)e/liers

Metered Dose *nhalers



!hronic Bronchitis



•!hronic infection and

inflammation of the/ronchi and /ronchioles.

•)arro6ing of air6ays de

to /ronchospasm,inflammation, and

infection.

•Bronchiectasis( air6ayslose cartilaginos

spport collect infectios

materials.




!hronic Bronchitis

4LBle Bloater5

Netter, F.H.

Respiratory

System. Volume

7, CIBA Collection

of Medical

Illustrations.

1979.

!hronic Bronchitis



Treatment.• Bronchodilators to treat

/ronchospasm.

• *nhaled corticosteroids totreat inflammation.

•%nti/iotics to treat

infection.

• Spplemental + to treat

hypo3ia.

&mphysema



• Destrction of alveolar

6alls.

• Decreased srface area

availa/le for gas

e3change.

• Decreased elastic

spport of air6ays.

• %ir6ay o/strction.

• Severe hyperinflation

often present.


&mphysema




Cest !"ra# of $m%#sema &'(in) (uffer*+




%ir6ay /strction in

& h 4 P 5




&mphysema 4↓Pel5

&mphysema



Treatment.• Bronchodilators to reverse

/ronchospasm.

• !orticosteroids forinflammation.

• %nti/iotics to treat infection.

• Diretics and digitalis to

treat right heart failre 4cor

plmonale5.

p y



% 0+'year old /oy



6as che6ing on his

pencil eraser tip.#e accidentally

s6allo6ed it.

#e coghed for

+'months.

Did he really

s'allo' the eraser

tipN



2etained 7oreign Body%spiration



• 7oreign /ody pts pressre on air6ay mcosa

compromises /loodflo6, and destroys air6ays.

• !hronic infection sets in, casing frther air6ay

destrction.

%spiration

Bronchiectasis



• %/normal dilatation of

/ronchi.

• *nvolves destrction of

cartilaginos 6alls.

• Most commonly de to

chronic infection.

• !an /e focal or diffse.

• %l6ays de to an

nderlying lng disease.



Bronchiectasis

Bronchiectasis



• !ommon in chronic lng

diseases.•!ystic 7i/rosis.

•Primary ciliary dyskinesia.

•*mmne deficiencies.•T/erclosis.

• !hronic infection destroys

cartilaginos air6ays.• /strctive lng disease.

• 2isk of massive

hemoptysis.

L? th hild h



L?oe the child 6ho

tastes salty from a kiss on the /ro6,

for he is he3ed,

and soon mst die. ''' Medieval German 7olk Saying

!ystic 7i/rosis



• Most common inherited

serios e3ocrinedisorder in !acasians.

• %tosomal recessive.

• Mltiple systems

involved.

• Most serios clinicalpro/lem and most

common case of death

is !7 lng disease.

• Discovery of the

!ystic 7i/rosis



!ystic 7i/rosis

gene in 0<@<.

• !ystic 7i/rosis

Transmem/rane

!ondctance

2eglator4!7T25 Protein.

• !hloride

channel ine3ocrine cells.

2ommens, :.M., et al.

Science, (4! 0-1<'0-@-, 0<@<.



Normal CF

Cl"H-

Na

L

Na

S L



H-

A S L

H-

H-H-

A S

Matsi, #., et al. Cell, )! 0--1'0-01, 0<<@.



!7 Bronchiectasis



!7



!ystic 7i/rosis

!ystic 7i/rosis#ome Plmonary Therapy



Median Srvival for !7 *mproves



0<O- 0<1- 0<=- 0<>- 0<@- 0<<- +--- +-0- +-+--

0-

+-

-

O-

1-

%ge 4years5

Pnemothora3



Pnemothora3 can arise from

rptred /llae or /le/s



Pnemothora3



Pnemothora3 in an *nfant



Tension Pnemothora3



7lid &3change inPlmonary !apillaries



•The alveolar'capillary

mem/rane is poros.

•7lid e3change canoccr across themem/rane.

•*n the lng, flidshold remain in thecapillary, not in thealveols.

•?hat forces keep flidin plmonarycapillariesN

Tisi, G.M. Pulmonary Physiology in Clinical

Medicine. ?illiams and ?ilkins, Baltimore, 0<@-.





!apillary %lveols

•↑ !apillary

hydrostaticpressre.

•↑ %lveolar

srface

tension.

•↑ !olloid

osmoticpressre.

•↑%lveolar

pressre.




Tisi, G.M. Pulmonary Physiology in Clinical

Medicine. ?illiams and ?ilkins, Baltimore, 0<@-.

• ↑↑ capillary

hydrostaticpressre pshes

flid into alveoli,

casing plmonary

edema.

• ↑ capillary

hydrostatic

pressre pshesflid into interstitial

space, casing stiff

lngs.

Plmonary $ymphatics



• 7lid is cleared

from the interstitialspace /y

lymphatics.

•Plmonary

lymphatics drain

throgh the hilm

to the thoracic dctin the sperior

vena cava.)etter, 7.#. Respiratory System. 9olme >, !*B%

!ollection of Medical *llstrations. 0<><.

#eart 7ailre andPlmonary &dema



/isi, 0.M. Pulmonary Physiology in Clinical

Medicine. illiams and il)ins, Baltimore, 1923.

$eft #eart 7ailre.

• Blood /acks p from theleft ventricle into the

lngs.

• *ncreases capillary

pressre.

2ight #eart 7ailre.

• Blood /acks p from

the right ventricle into

systemic veins.

• ↓ Thoracic dct flo6.

• ↓ Plmonary flid

clearance

•!lot travels from venos

Plmonary &m/olism



•!lot travels from venos

system to the lngs.

•!an case infarction of a

portion of lng.

•Massive P& can occlde

most or all of plmonaryotflo6 tract.

•!an case 2ight #eart

7ailre.

•!an case sdden death.

•2e8ires prompt diagnosis

and treatment.



•Deep venos throm/osis in

Plmonary &m/olism



•Deep venos throm/osis in

femoral veins is a common case.

•ther risk factors are

immo/iliation of legs for

prolonged periods.

•Signs and Symptoms(

•!ogh.

•!hest pain.

•Dyspnea.

•#ypo3ia.

•Treatment is anticoaglation.

%lthogh 6e have revie6ed a

$ng 2esponse to *nJry



%lthogh 6e have revie6ed a

nm/er of specific lng

diseases, the lng has only a

fe6 6ays to respond to

inJry.

• *nflammation.

• %ir6ay o/strction,

remodeling, and

/ronchiectasis.

• 7i/rosis.

• $oss of alveoli.

• 2epair 4retrn to normal

?hy the 2espiratory System isthe most important organ system



LTo kno6 even

one life has

/reathed easier

/ecase yohave lived ' that

is to have

scceeded.

2alph ?aldo &merson

0@-'0@@+

pulmonary pathophysiology

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