4.3 Non respiratory functions lung & shunt Flashcards
What is the fxn of type 2 alveolar cells
Production of surfactant
Stemm cell production type 1 cells
Type 1 are produced from type 2
Type 1 are thin
no signif barrier to gas exch
No ogranelles
dont divide
Lung damage -
2 divide to produce replacement
How are alveolar epithelial cells affected by oxygen toxicity
Thin Type 1 - easily damage high levels of oxygen
larger type 2 more resistant
Alveolar epithelium becomes thciker than normal - impariment of gas exchange
Oxygen conc return normal - type 2 prolif to replace 1`
What is surfactant
constitituents
Reduces surf tension - air liquid interface alveoli - redution larger in small alveoli
Stored type 2 alv cell - lamellar body
secreted into alveoli
Surfcat composite
Plip 80% - dipalmitoyl phophatdiyl choline
Neutral lipids 10%
Plasma proteins 4 %
Carbs 2%
severeal surfactant protiens 4%
What is the chemi feat dipalmitoly phophatdiyl choline - gives surface tension reduction activity
Ampipathic -
Charged Hydrophilic head - choline
hydrophobic tail - two palmitoyl groups
Struct feat - important orinetant of moleculs at air liq interface
What are the functions of surfactant
Reduce surface tension alveoli
- reduce effort
- mag dep conc on surf of fluid layer lining
when smaller - surf area smaller - conc surf - interface higher
radially dependent seufrace tension red agent - mag reduction tesnion depened radius aloveli
countract effects pred law lpalace - small alveoli higher pressure than large
improve stability
assist keeping dry
Oppose movement water from interstit to alveolar space
reducing collapse alvoli - reduce hydrostaitc pressure in tissue outside capillary
Roles surfactant proteins
4 specific protien found a- d
sp a sp b sp c sp d
sp b sp c - hydrophobic - neccessary spreading phospholipid into a monolayer lining alveoli
Sp a sp d -hydrophilic sp a- faciltate spread sp b - break lamellar body prevent plasma pro entry into fluid macophage enhancement regul8 surfactant turnover
Non respiratory fxn lung
1 Blood resevor 2 blood filtration - thrombi removed b4 brain 3 Metabolic -surfactant -protein collagen + elastin -r/o proteases a1at - metabol vasoactives 4 immunlog - macopahge iga 5 heat reg 6 air flow - facil speech 7 Drugs - rout admin some drugs -
Mech as blood resevoir
Vol lying
standing
vol capillary
Increase in PA pressure - increase vol blood lung - increase bentral blood vol
Recuitment - more vessels open
distenion - open bet bigger
Vol 450 lying
standing 250
Vol capillary 80
What is central blood volume
Volume blood in heart and lungs
errect 15%
lungs 450. heart 350 = 800
What way is pulmonary circ different?
1 Whole of CO - RV
Most blood traverese capillary
lung receives venous efflent whole body - mix ven blood
cap bed filter whole VR - only capillary bed capable of same
Second
Pulmonary circulation reacts low Po2 - constricting - HPV
Redirect blood away poorly vent alveoli
response system opp - vdilates
Perip vdil aim increase o2 supply / blood flow
Higher flow at lower pressure and vascular resistance
What is converting enzyme
ACE located pul cap endothel cell
2 fxn
1 Converts Ang I to active ang II - ang convertin enxyme
drugs which inhib ace - useful antihtn
Inactivaing bradkinin - inhib of fxn - lead ace side effect
eg angioed cough
Widely distrib body - lower conc than capillary
How are the vasoactives handled by lung
Activate aAng I
Inact Bradykin
Taken up 5HT, PGE2, PGF2, LK
Unaffected AngII pGA ADH, Adrenaline
What is the role in heat regulation
Upper resp tract fxn
upper aiwrway warm and humidfy gas to inspire gas to body temp
Obiltory loss of heat by route - latent heat vpa
req for evap water
eheat loss .58kcals per gram water ecap
daily resp insense water loss 400mls heat loss 230 kcal day
12%
What are major defency mech protect lung
Physical
1 upper airway filter mech & particle impaction
2 Airway reflex cough sneeze
3 Mucocillary escalator
Cellular mech
Alveolar macrophage
Iga - immun fact
Respiratory response to altitude
what is percent o2 air at 5500m
380mmhg where ambient pressure 1/2 sea level
Percent oxygen still 21%
Partial pressure oxygen air less
as ambient pressure is half
ambient po2 is 80 (.21x380) in dry
or 69 in saturated
What Po2 would you predict if alveolar vent was same as sea level
PAO2 = Pi - PACO2/r
= .21 (380-47) - 40/.8
= 20mmHg in absence in change of centilation
What vent response to asecnt to 5500
Hypoxameia - stim periph chemo rec - ventilation increase signifcantly
Resultts fall PaCo2 - acts central cehemo rec - inhibt chemorec in resp centre - limit vent rise
Action of fall in art Pco2 - d/t local brain ECF [H]
over days - bec equil accross bbb - preogres resotre ecf H to normal
Inhbi to increase in vent progress removed
vent rises marfkedy increase alveolar Po2 - decrease PCo2 - typcall takes secereal days before max response achieved (can inc x5)
What else involved acclimiatisation to altitude hypoxia
Increase oxygen uptake
increase tport and delivery
the above 2
increase Hb conc - hypx stim epo - may increase >20
Increase caplarry in muscle to failatte perfusion
Positon ODC alter -
left shift - hypocap
right shift inc 2 3 dpg -
Oxygen loading - decrease combo low alverolar po2 and right shift cyrve
Polycthtme - incr blood viscosity
HPV d/t low alv Po2 - increase PA pressures
Both - increase work / strain rihgt heart
PHTN & RV hypertrophy may occur
CO increase by 20 to 50% on ascent to altitude
as vent and Hb inc - co return normal
people live life altitude - high conc oxidative enzymes - great ability utilise oxygen
increase oxygen utilisation
Functions nose
what structural features assist
Pathway for bulk flow gas
smell
conditioning ventilated gas
Minimisation water loss resp tract
Eustachian tube enter nose
Major process condition inspired gas -
Humidification
Warming
removal particulate matter
All - assisted turbulent flow
increase surf area - turbinates
min water loss during expiate
moisture condense during expiration
-would lose 75% daily water intake if turbinates mechansim
warming and humid related - increase in temp increase amt water vapour req fully sat the air
Processes involved removing particulate
filtration:
hair
impaction on muscoa
sedimentation lim nose -
important in trachea and large bronchi
How much total airways resistance d/t the nose -
Major contributr and ressitance increase and insp flow rate increase
Mouth function low resistance bypass - short activation time
Resistance slows expiration help main lung vol and prevent atelectasis - phys peep
resistant - internal shape and feautres - favour turbulent flow
Functions of rbcs
1 Tport of oxygen
2 co2 tport
3 a b buffer
4 package hb
hb also carry NO - affinity reduc deoxy = release NO periph
How are function interrelated
Hb - 3 roles -
Haldane effect of o2 sat of hb on co2 tport
hb carbamino - imporant co2 tport
Bohr effect- pco2 and ph on o2 tport
hb buffer - imporntant co2 tport and ab balance
buffering affect degree sat - hb
carbonic anhydrase inside rcc
What are advantage of having Hb locate in RCC
package of hb
Protect fo filt
enverino raise p50 26.6 - allosteric effect 2 3 dpg which phys more advant
avoid icnrease plasma oncotic pressure if hb in solution
assist mainta as stable teatrae - posit coop
main same locn carbonic anyhdrase
return methb - back to hb - methb reduct in rcc cyto
Role RCC CO2 tport
Co2 tport in 3 forms in blood70% bic lelavce1 dissolved 2 bic 90% - accounbts 60% av diff co2 content 3 carbamino
RCC import
1 anyhdrase in red cell not plasma
2 Hb forms carbamino compoinds
3 hb buffer H production bic
Bic formed from co2 and water - carbon anhydrase catalyses
Fast
70% bic leaves RCC - hambuger- exchange Cl (cl shif)
Maintain elec neutraility
Hion production reaction
increase H disav - not removed limit bic production ( las mass action)
Addit low ph inhib prod 2 3 dpg
H is buffer by Hb
oxygen unloading facilate process - deoxy is ab tetr buffer than oxy
imidazole grooup 6.8 pka - histdine responsible most buffer
hb large no histidine residue (38) - designed buffer
Carbammino comnpound account 5% CO2 carriage contib 30% av diff co2 content
more imporrartant tport in venous blood -
compound formed combo co2 terminal aminos
Net prod H low pka carbamic acid
Formed with hb nad plasma protein
hb presnet 2x conc pl portein
Haldane effect
- increase co2 carry at same pco2 in deoxy v oxy
doexy 3/5 x more carbamino compared to oxy
- account 70% haldane effect
Secon dfacotr - ncrease buffering ability deox- mops H+ formed production bic
More bic formed because of buffering
some dissolved co2 present co2
Role RCC in AB meatbolsim
Hb - high contc many histide reside - suiot pka buffer phys ph
doexy better buffer - than oxy
buffer H prod from carb anyhdrse in rcc bic buffer cant buffer itsekf
What is role of RCC membrane
Gas tfer - oxy co
tfer bic to plamsa
cl shift
prote hb - glom fil stable
immunolog function rcc naito abo
Mechanics breathing
What are the muscle involved in ventilation?
Inspiration is active - d/ tcontract diaphragm
- contract Ex IC also cintrib
Diaphr respo 70% TV - traonctacion msucle causes intrapleeural - more eng - decrease alveolar pressure
gradient for inspiration dfiff alveolar and mouth pressure
Diaphr lower rib c3-c5
External contract ribs move up and forward
buckel hand increase tb diagram pump handle increase AP dap
TV not impair if ext IC paralysed
How much does dipahgram desed during tv and vc
TV - 1 cm
VC 10c,
What is oxygen cost normal TV at rest
3mls o2 min
1% consump
Why do we breath out
How diff exercise
Normal exp - passive
no active contraction - active require energy
energy elastic recoil lungs
during inspiration elastic potentinal energy in lung increase
with expriation - elastic potential energy used gen pressure gradient driving expiration - pull chest wall back to FRC
work expiration powered by inspiratory muscle - intermed store elastic pot energy lungs
exercise
rectas abd
int ext obliq tv and inter itercostal
What pressure gradient driving expiration
diff alvoelar press and mouth pressure
Normal TB peak alveolar +1cm
mouth pressure atm - 0 gauge
Whats respons for elastic recoil of lung
Factors responsible -
1 Surface tension of thin film of fluid lining alveolus
70%
surfactant - reduces reduction marked smaller size
2 Stretch elastic fibre in lung parenchyma fibres elastin collagent
Alveolar Arterial pO2 gradient
What is A a gradient
Num diff alve and art po2
PiO2 - PaO2
Ox tension difference ref to dA-aO2
What is ideal alveolar Po2
Ideal alveolar pO2 - Po2 present in alveoli -
No V/Q inequality in lung
+
Lung exchange gas same rate resp exchange ratio as real lung
Calc from alveolar gas eqn
What is use of A-a gradient
Index amt v/q mm and shunting
What need to know calc Aa
Inspired Oxy blood gas result
pAo2 - alve gas eqn
pao2 measured from blood gas
What factors affecting A-a
Normal values
What causes this gradient
VQ mm
Shunt
Diffiusion abnorm
Usually 5mmHg in young fit health
values 15mmHg - breathing room air acceptable
Value - higher in healthy elderly - no disease state
V/Q mm or scatter vq ratio
Shunt - small amount noirmal shunt bornch circ and thebesian vein drain left heart
diffusion
End pulm cap same Po2 alveolus - wall pases
extreme stress - path A-A d.t diffusion prob
-
Is Aa same in adults and pead
Neotates higher 30mmhg
increase venous admix shunt v/q scatter
Amount intrapulmonary shunt higerh - unexpaind / fluid alveoli
alveoili low vq common
Frc < CC - gas trapping occurs - normal tv
Art Po2 neonates - lower above but effect o2 delivery offset
Increase affinity Hbf
Increase CO
Increase HB after birth
HbF - 80% hb in neonates
Neoanates higher o2 consump 6mls kg min vs 3-3.5
How does v/q MM cause increase a-a grad
Lungs unit at apex - high v/q
end cap blood high Po2
not signif increase from blood - hb alm cmplete sat
Lungs base - lower v/q
conseq end cap blood drain lower Po2 than apex
lower po2 -a/w lower oxygen content as o2 sat of hb sligh decrease
total perfusion of basal units higher - perfusion base lower o2 content contrib more toal flow
lower Pv art Po2 -
SUMMARY
High V/Q apex - not contrib extra oxygen - flat curve
also doesnt contrib much flow
Low v/q base contrib flow at lower Po2
base most imporant effect and causes lowering art PO2 - increase Aa grad
Flow apex - not compenaste lowering - high po2 doesnt contrib compenaste increase oxygen
apical flow small
In patients w/ lung disease and icnreased scatter of V/Q rations
do unit high v/q ratios and units low v/q ratio contribute to increased Aa grad
Yes
maginutide contribute lung units to increase Aa can be estimated
Contribution units low Cq - assesd mesaure phys shunt w/ shunt eqn
Cintrib high v/q - assesed measure phs dead space -using bohr
Type analysis - approximation based asusmption lung
Increased Aa gradeint - decrease art po2 a/w increase pco2?
No
Increase art pco2 - sense central and perip increase vent
resore art pco2 normal
pco2 only eleveated additional factor impar pco2 feedback control
Reason icnrease alve vent restore pco2 - linear slope co2 dissoc curve
increase vent - decrease co2 content blood - some area lung compensate increase co2 cotnent blood underventilated
different situation oxygen flater upper part oxyhb mean increase cent not add adit oxygen compensate decrease content
Hypoxaemia vs hypoxia
Hypoxia - Presence tissue low enough adverse affect on tissue fxn
hypomaemia - abnormally low Po2 in arterial blood
Classify hypoxia
Hypoxic hypoxia -
gypoxia d/t low blood po2
Anaemic hypoxia
D.t inadeq tissue delivery oxygen by hb w. anaemia of CO pois
Circ hypxoia
inadeq blood flow to tissue - critical fall in Po2
may affect whole body
certain part - tonrinquet
Histotoxic
Why does hypovent cause hypoxaemia
Whats effect art pco2
Hypovent - less o2 deliver to and less co2 removed
rise alverolar pco2 pred pco2 inversel relate to alv vent
Fall alveolar Po2 - det use gas eqn
PAO2 - Pi - PACO2 / R
Eg - alv vent halved - doublin paco2 - inverse relationship
0.21 x 760-47 - 80.8
= 50
Art po2 lower - tissue po2 lower than that
Histotoxic hypoxia
Tissue are not able use oxygen normal
cyanide pois
binds inhib mito cytoo x
ox cant react w/ H deliver from ETPch - oxy phosp halt
Noted tissue po2 normal or elveated - impar oxy utilasation
Opp other forms
prime cause decerased o2 cell is decrease oxygen
Doent fit defn
revised
Oxygen substrat cyto oxidase
enz end etcp
All tissue effects of hypoxia - lack avial energy form atp block ox phosphrylaton
new defn
hpyoxia oxidative phosprhylation stops d/t inadeq utilisation of oxygen
crtil low cell po2 1-2mmHg
level pasetru point
very high oxygen affin for xyto oxidase
rxn continue until nearly all o2 gone
histotox hypica - ox phosp block - orimary effect on ETC
What phsyiological effect walk into room 100% N2 - close door
Hypoxaemia & anoxic hypxia
cyanosed
distressed death min
initial affect art po2 drop - no oxygen in inspired gas
po2 <50mmhg - peripher chemo repsond - vent progres increase
increase washout of o2 lung
frc major store
other effect
cerbral hypoxia - brain tisue lac admosis
central chemo respond to stim resp centre
cerenbgral hpyoxia - depression brai unconcuouss death
circ effect
autoreg - vasil near all tiuse increease flow vr and co
vasocn - cerbral - overom hypocapnioa cbf incrase
Carotid ody stim - severe brady - hypoxic brady
increase RR - increase Symp stim - increase hr - masks direct brady
HPV - rise in PApressure
cerebral hypox - symp stim - rise arterial bp - cushing reflex
Hypoxia - results depresion metaboims all cell
high oxgen affinity cyto oxidase - mito ox phospho contin down to po2 of 1 - pasteru
muscle internal small oxygen store omyoglobin
many tissues can derive additonal energy anearobi meatob 0 intracell acidosis
brain tissue most suecctile hypox and anox brain - coma death minutes
Shunt
What is the venous admixture
Term intechange shunt
shunt - blood enter aterial system wihtout passing thru ventilated area lung
ture shunt
po2 blood diff po2 mix venous blood
most cases po2 true shunt lower po2 blood - contrib depress art po2
Venous admix - amount mix venous blod added to pulm end capillary blood - produce obesreved drop art po2 from po2 in end capillary
n
Normally healthy peorosn two main source blood
contribu venous admix - blood true shunt
bronch benous blood - bronch circ
blood thebesida - blood not mix venous blood not expect po2 same mix venous
blood alveoli v/q <1
blood not fully oxygntead - passes poorly vent area lung
not true shunt - passed some ventilation
really v/q mm
Virtual shunt
Blood source - drop art po2
neither venous mdmix mixed venous blood
amt venous admix calc shunt eqn
value obtain
- lable virtual shunt
defined amount shunt present if shunt enitrely mix venous blood
amt shunt fully accoutn drop art oxygen content
advantage estimate venous admix obtain - monitor patient clin usefu no easy way calc true shunt no alternat use virtual shunt
noted smome case ssunt will bbe mix venous blood
mix ven blood shunt are lung not veniltaed
this case venous admix - shunt will be same
How can shunt eqn be calulatied
Qs/Qt = (CC’O2 - CaO2)/(CC’O2-CvO2)
eqn calc amt shunt of mix venous blood
Actual blood shunt may diff comp
value - not accurate in these esitn
normal sitation
shunt present bronchial circulation
thebesian vessel - lv compositon diff mix venous blood
Summary
shunt eqn based assumption
shunted blood has same com as mix venous blood
gives measure amt mix venous blood if added to end cap blood produce observed epression in art Po2 - virtual or as if shunt - true shunt not measure by eqn
How is shunt eqn derived
Bloods that shunt mix venous blood
CO Qt
= sum of shunt blood flow Qs +
blood flow thru lung Qt-Qs
total oxygen delivery - to body is CO by art content
Qt x CaO2
Must be equal sum of oxygen deliver from shunt and lung
Hence
Qt xCao2 = Qs CCvO2 + Qt-Qs X CCo2
Solvng yields shield eqn
Draw page 155
must equal sum amt oxygen dleivery shunt from lung
diagr page 155
PVR
How does vascular resitance in Pulmonary circulation compare to systemic
General ft Pulm - low resistance circuit
Pressure drop only 10mMhg - mean PA - 15 Mean LAP 5
Yet flow is same as systemic circuit - ie Whole Cardiac output
Pul VR 1/10th SVR
AS pressure drop in SVR 100 - 10x higher
What are major factors affecting PVR
1 Hypoxic pulmonary vascon
2 Lung volume
3 PA Pressure
What is HPV
Vasoconstrictive low alveolar Po2 -
Alveolar Po2 - determins not art Po2
When Po2 falls in one part lung = decrease vent or atelac w/ mucus pplug - pulmonary vassels vasoconstrict -
shunt pulmonary blood away - underdentialted area - better vent areas lung
Match vent and perfusion
advantrage - maint o2 uptake
During early LVF _ congest and hypxia - cause hpv shunt to upper zone - pulmonary vascular redistrib
What circ HPV - interest anaetheitst
Effect volatile
One lung anaesthsia
Relationsip PVR and lung volume
High and low lung vol - PVR increase
PVR lowest - when lung vole close to FRC
Low lung vol - extra alveolar vessels - small diamter high resistance
as volume expands - wall pulled by elastic fibre in lung - and diameter increase
resistance decreases
As volume expands further
increased stretching distort and decrease diam of pum capillary - alveolar vessels - causes increase PVR
PVR higher at high and low lung vol - d/t different meachansms
PVR is at FRC
how does PAP pressure affect PVR
Increase PA pressure signif decrease PVR
Remark prop - how low PVR already
Recruitment and dsitension of pulm capil
What are measure required to calculate PVR using swan
PVR = MEAN PAP =PCWP x 80
____________________
CO
Vas resistance = input P - output P/ blood flow
Normal value 100 dynes sec
West zones
Zone 1: PA > Pa > Pv
MAy be present at top - if drop in BP - Inc PA - 2’ to IPPV - alveolar dead space
Zone 2: Pa > PA > Pv
Blow flow det diff b/w art & alveolar pressure - stralring resist mech - pulsatile
Zone 3: Pa > Pv > PA
FLow determ AV diffce
Distenion
Zone 4: Pa > Pi > Pv > PA
alveoli (PA), in the arteries (Pa), in the veins (Pv) and the pulmonary interstitial pressure (Pi) :
