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Flashcards in SM02 Mini1 Deck (658):

why do the sinoatrial nodal cells set heart rate?

set frequency of action potentials of heart muscle b/c they lack a stable membrane potential between successive action potentials

display progressive slow depolarization beteen action potentials 


what determines the primary pacemaker?

rate of phase 4 depolarization

fastest -> slowest: sinoatrial node, atrioventricular node, purkinje fibers


why is there a delay between atrial & ventricular contractions?

slower conduction velocity at the atrioventricular node

0.05 m/s compared to 1m/s thru the atria (coupled via gap junctions)

**functionally important for complete filling of ventricles to occur before contraction**


describe the electrical pathway in the heart

  1. action potential generated at sinoatrial node
  2. traverses right atrium & passes to left atrium via Bachmann's bundle
  3. atrioventricular node
  4. bundle of His
  5. R + L bundle branches to apex
  6. up walls of ventricles via Purkinje fibers


Nernst potential for sodium



Nernst potential for potassium



Nernst potential for calcium



result of fast voltage gated Na+ channels in cardiac tissue

activated at -70mV

rapid opening via m gate & rapid closure via h gate

inward membrane current

depolarizes cell (increase of membrane potential/interior becomes more positive)


Kir 2.1

aka inward rectifier

opens at negative voltages

sets stable negatie reting membrane potential of atrial & ventricular muscles cells

close as membrane potential becomes more positive



aka transient outward K+ current

opens rapidly upon depolarization of membrane

closes rapidly generating transient repolarizing force in ventricular & atrial muscle


IKr & IKs

aka rapid & slow components of delayed rectifier K+ current

closed at negative voltages

open when membrane potential becomes more +

mainly responsible for repolarization of action potentials in heart


difference between IKr & IKs

IKr has faster inactivation rate than IKs

IKr current is larger→ more important current in facilitating repolarization of action potentials


T-type calcium ion channels

Tiny conductance & Transient openings

predominantly in pacemaker & atrial tissue

open at -55mV

inactivate fairly rapidly

relatively small conductance compared to L-type


L-type calcium ion channels

Large conductance & Long Lasting openings

found throughout heart

open @ -40mV

inactivate more slowly comapred to T-type



cardiac ion channels

  • Na+: fast voltage gated Na+ channels
    • inward flow→ depolarizes/increases potential
  • K+: Kir 2.1, Ito, IKr, IKs
    • outward flow→ repolarizes/decreases potential
  • Ca2+: T-type & L-type (predominant)
    • inward flow→ depolarizes/increases potential



aka Funny current

mixed conductance channel

permeable to Na+ & K+ 

activated by hyperpolarization (@ - membrane potentials) & cAMP (ligand gated)

small conductance channel

@-60mV, driving force of Na+ influx greater than K+efflux


importance of NCX

aka sodium calcium exchange antiporter

3 Na+ influx w/1 Ca2+ out

generates inward membrane current by charge difference (electrogenic)

removes Ca2+ during muscle relaxation


what ion channels are not present at the sinoatrial node & the effect?

Kir 2.1 (inward rectifier K+ channels)

no stable resting membrane potential during phase 4


maximum diastolic potential

most negative membrane potential observed in SA or AV nodal cells


Phase 0 of nodal action potential

aka upstroke

produced by opening of voltage-dependent L-type Ca2+ channels

causes influx of Ca2+

threshold of -40mV



Phase 3 of nodal action potential

aka repolarization

produced by closure of L-type Ca2+ channels & opening of delayed rectifier IKr & IKs 

stops influx of Ca2+ & efflux of K+


Phase 4 of nodal action potential

aka pacemaker potential

membrane potential more negative→ IKr & IKs close & funny channels open→ stop movement of K+ & influx of Na+

membrane potenial increases

@ -55mV T-type Ca2+ channels open→continues depolarization

@ -40mV L-type Ca2+ channels open starting phase 0


Phase 0 of ventricular action potential

aka upstroke


opening of fast voltage-dependent Na+ channels→ influx of Na+→ depolarization

as membrane potential becomes more +, Kir 2.1 channels close→ membrane less permeable to K+


phase 1 of ventricular action potential

aka early repolarization

produced bu closure of fast voltage-gated Na+ channels

opening of transient outward voltage-gated K+ channels (Ito)


phase 2 of ventricular action potential

aka plateau

opening of voltage-dependent slow L-type Ca2+ channels→ influx of Ca2+

downward slope produced by opening of slow delayed rectifier K+ channels (IKs)→ efflux of K+

NCX antiport also contributes maintaining the plateau


Phase 3 of ventricular action potential

aka rapid repolarization

produced by closure of L-type Ca2+ channels & opening of several K+ channels

IKs & IKr open until reaching -60mV

Kir 2.1 complete final phase of repolarization


phase 4 of ventricular action potential

aka resting membrane potential

IKs & IKr are closed

Kir 2.1 (inward rectifier) remains open & maintains resting membrane potential


why are epicardial action potentials shorter in duration than endocardial action potentials?

greater expression of Ito (transient outward K+ channels)→ creates phase 1 notch

depolarization spreads endo to epi & repolarization spreads epi to endo→ thus epi must be shorter→ stops adjacent cells from reactivating those surrounding them


intrinsic firing frequencies of pacemaker cells

sinoatrial cells= 60-100 bpm

atrioventricular cells= 40-60 bpm

Purkinje cells= 20-40 bpm



rapid firing of sinoatrial node causes secondary (AV node) & tertiary (Purkinje) pacemakers to fire at SA node rate (faster than their intrinsic rates)


what current(s) contribute to the action potential in both SA node & ventricular cells?

L-type Ca2+ current



protein that binds Ca2+ in SR

closely associated w/SR terminal cisternae


why are T-tubules wider in cardiac tissue than skeletal?

to reduce the prospect of Ca2+ ion depletion


where are L-type Ca2+ channels located?

aka DHPR (dihydropyridine receptors) & CaV 1.2

sarcolemma along T-tubule

about 30% of Ca2+ for each contraction enters this way


methods for restoration of Ca2+ after cardiac muscle contraction

  • reuptake by sarcoplasmic reticulum via SERCA2 pump (70%)
  • removed from cell by NCX exchanger (28%)
  • removed from cell by plasmalemmal Ca2+ ATPase (2%)


describe mechanism of Ca2+ reuptake by the sarcoplasmic reticulum

SERCA2 (sarcoplasmic endoplasmic reticulum calcium ATPase) regulated by phospholamban

phospholamban dissociates from SERCA2 when phosphorylated at ser16 by PKA & thr17 by CaM kinase II

phospholamban dissociation increases rate of Ca uptake


similarities between skeletal & cardiac muscle

  • striated
  • interdigitating thin & thick filaments displaying A & I bands
  • thin filament regulatory proteins: tropomysosin & troponin
  • cross bridge cycle is identical


differences between cardiac & skeletal muscle

  • wider T-tubules in cardiac muscle
  • T-tubules enter at Z-lines in cadiac muscle
  • mechanism of Ca2+ release from sarcoplasmic reticulum
  • fewer DHPRs in cardiac muscle
  • Ca2+ doesn't enter skeletal muscle & thus doesn't need to be removed
  • Skeletal DHPR= CaV 1.1/Cardiac DHPR=CaV 1.2
  • Skeletal RyR1/Cardiac RyR2
    • no physical connection between DHPR & RyR in cardiac


sites of of ATP usage in cardiac muscle

  • bind S1 myosin head for cross bridge cycle
  • SERCA2 
  • PMCA: remove Ca2+ from cell
  • Na+/K+ ATPase
  • adenylate cyclase (AC)


what are the primary metabolites utilized by the normal adult heart?

free fatty acids (60-70%) & carbohydrates


what is the advantage(s) of the long plateau observed in ventricular muscle action potentials?

for every contraction period (systole), there is a resting period (diastole) during which the heart can refill w/blood


why can't cardiac muscle remain in a state of sustained (tetanic) contraction?

b/c cardiac muscle AP duration is musch longer→ longer refractory period

fast sodium current inactivates rapidly, but cannot be reactivated until negative membrane potentials are reached (-70mV) during repolarization


optimal length


narrow range of whole-muscle stretched lengthin which active tension is maximal



cardiac muscle cells are relaxed 

cytoplsmic Ca2+ is very low

blood enters ventricles


how is passive tension generated in ventricular muscle?

blood entering the ventricles stretches the cells to increase volume

titin is grestest contributor (same as in skeletal muscle)



aka end diastolic volume

volume in the vnetricle at the end of the diastolic phase


what is the difference in normal working range between skeletal & cardiac muscle?

skeletal= total tension ranges around optimal length

cardiac= below optimal length


Frank-Starling Law

stroke volume of the heart increases in response to an increase in the volume of blood filling the heart (the end diastolic volume) when all other factors remain constant



in left ventricle= aortic diastolic pressure

load the muscle must overcome to open the aortic valve & eject blood

when ventricular pressure exceeds afterload→ aortic valve opens


what is the only limiting factor of Vmax of ventricular shortening velocity?

myosin ATPase


what happens to shortening velocity for a certain afterload as preload increases?

shortening load will increase

blood ejected faster b/c force of contraction is increased


how can Vmax (velocity of shortening) be increased?

increased inotropic status

ex. increase in sympathetic stuimulation



theoretical afterload (aortic pressure) so high that muscle cannot contract


how can Fmax be increased?

increased inotropic status

ex. increase in sympathetic stimulation


effects of increased preload

  1. increased velocity of shortening at a given afterload
  2. increased Fmax w/o changing Vmax


effects of increasing inotropy

  1. increases velocity of shortening at a given afterload
  2. increases Fmax & Vmax


how is an electrocardiogram recorded?

epicardial cells are + compared to endocardial cells when heart is at rest

during AP: epicardial cells change from + to - → this change is recorded by ECG

conducted change is recorded via extracellular fluid to the surface of the skin

electrodes detect movement or spread of electrical activity throughout the heart

recorded signal is much smaller than reality


what causes a positive deflection to be recorded?

 depolarization (action potential) toward the positive electrode (cathode)


repolarization traveling away form positive electrode


what is recorded when the whole tissue is depolarized?

a flat line at the isoelectric point

b/c there is no potential difference to measure between two points


what causes a negative deflection to be recorded?

depolarization (action potential) travelling away from positive electrode


repolarization travelling toward positive electrode


Einthoven's triangle

arrangement of standard limb leads (I, II, & III)

records electrical activity in frontal plane through heart


Dr Einthoven invented first practical ECG in 1903


Lead I

+ electrode on LA

- electrode on RA

0º horizontal plane; bipolar lead


Lead II

+ electrode on LL

- electrode on RA


Lead III

+ electrode on LL

- electrode on LA


what physiological event corresponds to the P wave?

atrial depolarization→ contraction of atria

depolarization as AP spreads away from SA node throughout atria @ 1m/s

speed due to gap junction connectivity througout atria

1st 1/3 is RA depolarization, 2nd 1/3 is RA & LA depolarization, & 3rd 1/3 is LA depolarization b/c RA depolarizes 1st


what physiological event corresponds to the QRS complex?

ventricular depolarization→ventricular contraction

depolarization (AP) spreads down bundle branches to apex @ 5m/s

results in positive deflection= R wave

normal 0.08-0.10seconds

atrial repolarization is also occuring, but obscured by signal from ventricles


what physiological event corresponds to the ST segment?

period of time that the ventricles are fully depolarized

duration of plateau phase of ventricular action potential

last about 120sec

elevated in MI

depressed when heart is hypoxic (coronary insufficiency)


what physiological event corresponds to the T wave?

ventricular repolarization


what physiological event corresponds to the QT interval?

period from beginning of ventricular depolarization to end of ventricular repolarization

ventricular systole takes place

normal <400ms (0.4 seconds)


what physiological event corresponds to the PR segment?

AP slowly (0.05m/s) transmitted thru AV node

electrically neutral period


what is the most important factor to analyze about segments?

change from the isoelectric line


what is the most important factor to analyze about intervals?



what physiological event corresponds to the PQ/PR interval?

P wave & PR segment

time between atrial excitation & beginning of ventricular excitation

normal is 0.12-0.20

shortens w/increased HR & lengthens w/decreased HR

>0.20 seconds→AV conductions block (AV node of bundle of His)


what physiological event corresponds to the Q deflection?

spread of the AP across the interventricular septum from L to R

seen on lead II, but not all leads


what physiological event occurs R→S?

downward deflection created by depolarization (AP) moving away from positive electrode (apex)

dominated by larger L ventricle


what physiological event corresponds to the T wave?

results from ventricular repolarization

base 1st/apex last

+ deflection created by dominant repolarization moving away form + electrode

typically lasts 160ms

broader w/lower amplitude b/c repolarization is slower than depolarization & less unidirectional


segment v. interval

segments are on isoelectric line

intervals include a waveform


how does coronary insufficiency present on an ECG?

ST segment depression


what is a subendocardial infarct?

infarct does not affect teh full thickness of L ventricular wall


what can cause a prolonged QT interval?

myocardial damage

coronary ischema

conduction abnormalities: genetic syndromes including long QT


Long QT

many causes

predisposes to ventricular arrhythmias

delays repolarization phase in ventricualr tissue


cause of LQTS1

loss of function of IKs


cause of LQTS2

loss of function IKr


cause of LQTS3

gain of function to INa

faster upstroke of ventricular action potential


what physiological event corresponds to the TP segment?

heart totally quiescent


heart refills w/blood


which wire plays no role in the ECG waveforms?


it's neutral lead

exisits to complete the electrical circuit only


how are augmented limb leads created?

electrical signal from 2 limb electrodes is simultaneously fed into negative terminal

produces and average signal located roughly in the middle of the chest



augmented Vector Left


-RA & -LL




augmented Vector Right


-LA & -LL




augment Vector (left) Foot


-RA & -LA



precordial leads

chest leads

all +

share common negative= Wilson's central terminal

record electrical activity in transverse plane thru heart

progression from - QRS @ V1 to + QRS @ V6


time segments on ECG trace paper

on horizontal axis

small block= 0.04 sec

large block= 0.2 sec


voltage segments on ECG trace paper

on vertical axis

small block= 0.1mV

large block= 0.5mV


what does the height of QRS complex tell us?

greater height of QRS complex→ more aligned spread of depolarization on a particular vector

if spread of depolarization is directly towards a lead, then QRS will be most + on that lead


exact calculation of heart rate from ECG trace

(# of small blocks * 0.04sec)= (x seconds/beat)

(60 seconds/minute) / (x seconds/beat)= bpm


quick estimate of HR by ECG trace paper

  • 1 large block= 300
  • 2 large block= 150
  • 3 large block= 100
  • 4 large block= 75
  • 5 large block= 60
  • 6 large block= 50
  • 7 large block= 43
  • 8 large block= 37


normal PR interval

0.12-0.20 seconds


normal QRS complex duration

0.10 seconds


normal QT interval duration

<1/2 RR interval at rest


normal sinus rhythm

1:1:1 ratio P wave: QRS complex: T wave

  • rhythm: regular
  • rate: 60-99bpm
  • QRS duration: normal (<0.10seconds [3 small blocks])
  • P wave: visible before each QRS
  • PR interval: normal (0.12-0.20 seconds/<5small blocks)


junctional rhythm

 SA node is not functional→ AV node is primary pacemaker→ inverted or no P waves

  • rhythm: regular
  • rate: 40-60bpm
  • QRS duration: normal
  • P wave: inverted in lead II or not visible


sinus tachycardia

  • rhythm: regular
  • rate: >100bpm
  • QRS duration: normal (<0.10seconds [3 small blocks])
  • P wave: visible before each QRS
  • PR interval: normal (0.12-0.20 seconds/<5small blocks)

causes: (sympathetic innervation), exercise, fever


sinus bradycardia

  • rhythm: regular
  • rate: <60bpm
  • QRS duration: normal (<0.10seconds [3 small blocks])
  • P wave: visible before each QRS
  • PR interval: normal (0.12-0.20 seconds/<5small blocks)

causes: (parasympathetic innervation), highly trained athletes, pts on beta blockers


Long QT syndrome ECG

normal QT interval duration= 400ms

QTc (men)= 450ms/QTc (women)= 470ms

corrected by Bazzett's formula: QTc= QT duration/ square root(RR interval [HR])


1º AV block

first degree atrioventricular conduction block

partial block of AV node→ slower conduction thru AV node

  • rhythm: regular
  • rate: 60-99bpm
  • QRS duration: normal (<0.10seconds [3 small blocks])
  • P wave: visible before each QRS
  • PR interval: >0.20 seconds/>5small blocks)

causes: fibrosis, inferior MI, OR induced by enhanced vagal tone, athletic training, beta blockers, Ca2+channel blockers (can be normal finding)

tx: none needed, but may increase risk of more serious heart block types


Wenkebach's heart block

Mobitz type I 2º heart block

pregressive lengthening of PR interval w/each beat until P wave fails to result in QRS complex then resets

cause: conduction block in AV node

tx: usually benign→ seen in children, athletes, pt w/elevated vagal tone


2º heart block

PR interval: > 0.25 seconds (>6 small blocks)

sometimes, not always conduction thru AV node fails→ P wave occurs, but does not produce QRS complex

intermittent conduction failure w/subsequent loss of ventricular contraction


Mobitz type II 2º heart block

no lengthening of PR interval

sudden, unexpected loss of AV conduction & ventricular activation

wide QRS b/c excitation is spreading cell-to-cell instead of thru the His-Purkinje system

more dangerous than Mobitz type I

could lead to cardiac arrest

tx: pacemaker implant


3º heart block

complete failure of conduction from atria to ventricles

no relation between P waves & ventricular contraction

  • rhythm: regular
  • rate: atria @ 60-99bpm/ventricles @ 20-40bpm
    • PP interval short than RR interval
  • QRS duration: broad QRS b/c excitation is spreading cell-to-cell instead of thru the His-Purkinje system
  • P wave: 2-4 for each QRS complex
  • PR interval: normal (0.12-0.20 seconds/<5small blocks)


Atrial Flutter

atrial focus activate atria NOT SA node

  • rhythm: regular
  • rate: usually>100bpm up to 300bpm
  • QRS duration: normal (<0.10seconds [3 small blocks])
  • P wave: repetitive, obscuring baseline
    • "saw tooth" appearance
    • 2-4/QRS complex


Atrial Fibrillation

lack of coordination between atria & ventricles

re-entry current occurring in atria

  • rhythm: irregularly irregular
  • P wave: none distinguishable

not directly fatal, but blood can pool in poorly mixed areas→ thrombus→ embolism


re-entry current

damaged/diseased cardiac tissue conducts so slowly that AP excites adjacent repolarized tissue

re-entry of AP

result: non-rhythmic cycyles of contraction & relaxation


Ventricular Fibrillation

re-entry current in ventricles

TOTAL absence of any pattern

arrythmic; no R waves to determine HR

result: decrease stroke volume to fatally low  level


where does a pulmonary embolism originate?

as a R atrium thrombus


what can occur if a thrombus is present in the left atria?

coronary or cerebral embolism→ MI or stroke


Monomorphic Ventricular Tachycardia

caused by irritable ventricular focus→ discharges premature impulses for 3+ beats w/o interruption

  • rhythm: regularly irregular
  • QRS duration: broader than normal b/c impulses are conducted cell-to-cell instead of His-Purkinje system
    • all look the same
  • no distinguishable P or T waves


Polymorphic Ventricular Tachycardia

beat-to-beat variation in QRS morphology

each ventricular impulse can be generated form a different place

QRS may be taller or wider

common type: Torsades de pointes

expect consultation needed


effects of ventricular tachycardia

decrease cardiac output→ hypotension, collapse, acute heart failure, & possible myocardial perfusion w/degeneration to ventricular failure

caused by extreme HRs & uncoordinated atrial contracrion

decreased cardiac output may also 



premature ventricular contractions originating in ventricles from foci w/in His-Purkinje system

  • rhythm: dependent on uni or multifocal
  • rate: any
  • QRS duration: broad, strangely shaped 
  • P wave: absent
  • PR interval: normal (0.12-0.20 seconds/<5small blocks)
  • T wave: - if net + QRS, or vice versa



3:1 PVC



2 PVC together surrounded by normal sinus rhythm



1:1 normal beat to PVC



2:1 normal to PVC beats


Wolff-Parkinson-White Syndrome

type of pre-excitation syndrome w/delta waves

consequence of abnormal conduction via accessory pathway across annulus fibrosus cordis (often Bundle of Kent)→ can conduct antergrade (rare), retrograde (15%), or both (in majority)

  • rhythm: regularly irregular
  • QRS duration: wide; >120ms
    • delta wave= slurred onset
  • P wave: visible before each QRS
  • PR interval: short; 0.<12 seconds; effectively absent
  • secondary ST or T wave changes



aka left bundle branch block

broad QRS

depolarization spread across septum reversed (R→L)

large - & elongated S waves in V1-V3

nothed or slurred R wave in V6

repolarization endo to epi (reversed)→ inverted T wave in V6



aka right bundle branch block

broad QRS

depolarization spread normal across spectum (L→R)

delayed depolarization of RV generated seconds R wave→ seen in V1

slurred Swave in V6

inverted T wave in V1


regular rhythm

RR interval are identical for wach heart beat

rhythm is maintained


regularly irregular rhythm

pattern of beats that repeats

2º heart block


irregularly irregular rhythm

no underlying regularity

inconsistent RR interval (HR)

ex. atrial fibrillation


define mean electrical axis (MEA) of heart & what is the normal range?

net direction of electrical conduction during ventricular depolarization

tells us:

  • orientation of heart
  • size of ventricular chanbers
  • conduction block

normal range= +90 to -30º


what change in MEA does right ventricular hypertrophy cause?

right axis deviation= +90 to +180º

CAN also be normal finding in children & tall thin adults

QRS is - in lead I & + in aVF


what are the cause(s) of right axis deviation?

  • normal in children & tall thin adults
  • right ventricular hypertrophy
  • chronic lung dz w/pulmonary HTN
  • pulmonary embolism


what change in MEA does left ventricular hypertrophy cause?

left axis deviation= -30 to -90º

QRS is + in lead I & - in lead II and aVF


what are the cause(s) of left axis deviation?

  • left ventricular hypertrophy
  • inferior MI
  • emphysema→ heart moved posteriorly due to hyperexpanded lung pushing L ventricle (thus MEA) into upper R quadrant


semi-quantitative method for determining MEA

  1. draw radial axis
  2. determine net + or - for lead I
  3. draw 90º arc in either direction from corresponding end of arrow
  4. repeat for all 6 limb leads
  5. 30º segment where all 6 lines are present is where the pt's MEA will be found


Net zero method for determining MEA

**only applicable if one limb lead shows net zero

  1. determine net zero lead
  2. go to perpendicular lead
  3. If QRS of perpendicular lead is net +, then + end is pt's MEA. If QRS of perpendicular lead is -, then -end is pt's MEA.


Quick & dirty method for MEA determination

  • normal MEA
    • Lead I= +
    • Lead aVF= +
  • Right axis deviation
    • Lead I= -
    • Lead aVF= +
  • left axis deviation
    • Lead I= +
    • Lead aVF= -


what occurs during phase 3 of the cardiac cycle? and what is the corresponding electrical event on the ECG?

atrial contraction

P wave tha induces atrial contraction occurs just before this phase


what phase of the cardiac cycles does the QRS complex preceed?

ventricular contraction/systole

phase 4-5


what electrical event on an ECG immediately preceeds phases 6-7 (ventricular relaxation/diastole)?

T wave


what event & cardiac phase is associated with the ST segment?

phase 5= rapid phase of ventricular ejection


what physical events occur during systole?

ventricular contraction & ejection


what physical events occur during diastole?

ventricular relaxation & filling phase


what happens when left artial pressure exceeds left ventricular pressure?

typically aroun 10mmHg

mitral valve opens

rapid passive filling of LV→ LV volume increases

aortic pressure is high b/c ventricle has just finished ejection phase & aortic valve closed


what is the approximate volume of left ventricular end systolic volume?



what phase of the cardiac cycle occur during diastole?

phases 1-3

  • 1: rapid ventricular filling
  • 2: diastasis (slow ventricular filling)
  • 3: atrial contraction
    • only contributes 5-10% of ventricular volume


a wave

wave of increased L atrial pressue on atrial pressure curve immediately following P wave on ECG

also causes small rise in ventricular pressure & volume

immediately followed by mitral valve closure


what created the S1 sound?

mitral valve closure


what begins systole?

mitral vavle closure

isovolumetric contraction phase (phase 4)


c wave

 positive deflection on atrial pressure curve due to teh bulging of the mitral valve into the atrium as the ventricle begins to contract


what causes the aortic vavle to open?

when left ventricular pressure exceeds aortic pressure

occurs during phase 5 aka rapid ventricular ejection phase


what reduces the rate of blood flow during the slow ventricular ejection (6) phase?

reduced ventricular pressure

due to reduced # of contracting cardiomyocytes as repolarization begins


 what phase is at the beginning of diastole?

isovolumetric relaxations (7) phase

marked also by the closing of the aortic valve that creast the S2 heart sound as it closes


what creates the S2 heart sound?

aortic valve closure


how are heart sounds produced?

the sudden stretching & subsequent vibration of compliant valves, surrounding connective tissue, & vessels creates sound

NOT the closure itself


Windkessel effect

transient increase in aortic pressure as blood starts to flow back into ventricle shutting the aortic valve cusps

turbulent flow helps support coronary circulation & creates dicrotic notch in aortic pressure curve


v wave

positive deflection of left atrial pressure curve created by atrial filling


venous pressure wave

jugular vein pressure waves created by events on R side of heart

  • a-wave: RA contraction
  • c-wave: tricuspid valve bulging into RA
  • x-descent: relaxation of RA
  • v-wave: filling of RA against closed tricuspid valve
  • y-descent: fall of jugular venous pressure due to rapid phase of ventricular filling


what does point A on a pressure-volume loop coorespond to?

end systolic volume

mitral valve opens


what does Phase I on a pressure-volume loop coorespond to?

rapid ventricular filling


atrial contraction


what does Point B on a pressure-volume loop coorespond to?

end diastolic volume (preload)

beginning of systole

mitral valve closes (S1 sound)



left ventricular wall stress at end of diastole

normally related to volume in LV at end of diastole


what does Phase II on a pressure-volume loop coorespond to?

isovolumteric contraction of left ventricle


what does Point C on a pressure-volume loop coorespond to?

aortic semi-lunar valve opens 

estimate of diastolic blood pressure (afterload)


what does Phase III on a pressure-volume loop coorespond to?

rapid phase of ventricular ejection

estimate of systolic BP (highest point of curve- estimate of maximal afterload pressure)

slow phase of ventricular ejection


what does Point D on a pressure-volume loop coorespond to?

aortic valve closes (w/S2 sound)

TRUE end systolic volume

same volume as A in health

marks beginning of ventricular diastole


what does Phase IV on a pressure-volume loop coorespond to?

isovolumetric relaxation


local blood flow

aka intrinsic blood flow

mechanisms by which individual organs control their own blood flow


metabolic regulation of blood flow

arterioles sense their external environment (interstitial fluids) for metabolites & paracrine agents & respond appropriately

cause local dilation or constriction


What are the metabolites that influence arteriolar blood flow?






what are the paracrine agents that influence arteriolar blood flow?

angiotensin II

Histamine (vasodilaton)


prostaglandins (F family→ constriction; E family→ dilation)


How does O2 concentration influence arteriolar blood flow?

decreased O2→ local dilation (to get more)


Does CO2 influence arteriolar blood flow? If so, how?


increased [CO2] in the interstitium→ local dilation (to carry out waste)


describe the myogenic reflex in relation to blood flow regulation.

  • increased blood flow
  • excessive stretch of blood vessels
  • stretch activated Na+ channels
  • depolarization of smooth muscle cells
    • L-type Ca2+ channels
  • smooth muscle cell contraction
    • vasoconstriction
  • decreased blood flow


How can NO production be stimulated?

  • paracrine agents
    • histamine via H1 receptors
    • ACh from cholinergic nerves
    • Bradykinin
  • increased sheer stress on luminal vessel wall (endothelial cells!!)
    • elevation of pressure gradient along long axis of vessel


What reaction does NO synthase catalyze?

L-arginine + O2 + NADPH→ citrulline + NO + NADP


How does NO travel from the epithelial cells to vascular smooth muscle?

simple diffusion b/c it is a lipophilic gas


How does increased [cGMP] lead to vasodilation?

  • increased cGMP
  • activation of protein kinase G (PKG)
  • phosphorylation of phospholamban
  • dissociation of phospholamban from SERCA2
  • SERCA2 increased rate of Ca2+ uptake
  • decreased contractility of vascular smooth muscle
  • vasodilation

PKG activation leads to inhibition of myosin light chain kinase reduced Ca2+ sensitivity of myofilaments→ relaxation


How do organs maintain a relatively constant blood flow regardless of perfusion pressure?


myogenic theory explains reduced flow in the presence of increased systemic HTN

metabolic theory explains the vasodilaton & increased flow that results after a sudden decline in perfusion pressure


What organs most clearly display autoregulation?

kidney, heart, & brain respectively


what organ(s) do not display autoregulation?

skin & pulmonary circulation


over what blood pressure range do the heart & brain maintain a constant flow?




incerased blood flow to different tissues of the body


active hyperemia

increase in blood flow due to an increase in metabolism

  • increased metabolism
  • increased release of metabolic vasodilators into extracellular fluid
  • dilation of arterioles
  • decreased resistance created increased blood flow
  • O2 & nutrient supply to tissue increases for duration of increased metabolism


functional hyperemia

aka exercise hyperemia

active hyperemia that occurs during exercise

mostly to type I (aerobic) myocytes

blood flow increass to 80-85% of cardiac output to skeletal muscle from normal of 15-20%


reactive hyperemia

increased blood flow & vasodilaton that occurs in reaction to short interruption of blood flow

temporary occlusion→ buildup of metabolic waste→ vasodilation

longer occlusion→ longer period of subsequent reactive hyperemia


what type of activity displays active hyperemia?

phasic exercise

ex. running


what type of activity displays reactive hyperemia?

occlusive muscle activity

ex. weight lifting


what mechanisms are involved in hyperemic reponse to exercise?

adenosine & K+

maybe sympathetic cholinergic fibers in exercise-induced vasodilation


why does sympathetic activation lead to coronary vasodilation?

  • stress induced SNS 
    • HR & SV increased
  • SNS alpha-1 adrengenic receptors→ vasoconstriction
  • active hyperemia caused by production of adenosine & NO 
  • vasodilation


when is reactive hyperemia observable in coronary blood flow?

during systole (contraction)

oddly this means that there is decreased flow when it is needed the most


when is left ventricular coronary blood flow highest & why?

during diastole

b/c ventricular muscle is relaxed→ coronary vessels are unobstructed


when is right ventricular coronary blood flow highest?

during systole

right ventricular does NOT contract w/as musch force as L→ right coronary flow is not impeded

coronary artery pressure rises during systole→ increases driving pressure & R coronary blood flow

less reactive hyperemia compared to left coronary arteries


at rest, approximately what percentage of O2 & cardiac output does the brain consume?

O2= 20%

cardiac output= 14%


what anatomical anstomosis helps to maintain cerebral blood flow?

Circle of Willis

created by the union of internal carotid arteries & basilar artery


how does cerebral blood flow increase?

  • increased brain activity
  • increased metabolic rate
  • raised arterial CO2 (hypercapnia)-- active hyperemia metabolite
  • vasodilation


cardiac input

aka venous return


what is required physiolgically for blood to return to the heart?

pressure gradient between the right atrium (approximately 2mmHg) & central venous pressure (CVP) (approximately 10mmHg)


why does a venous system pressure gradient of 8mmHg generally lead to a flow of 5L/min through the veins?

  • 8mmHg is average pressure gradient fro venous return
  • venous return= cardiac input
  • cardiac input= cardiac output
  • average cardiac output= 5L/min


what is the most important determinate of cardiac output?

venous return


what is the most important determinate of venous return?

central venous pressure


what happens to venous return when right atrial pressure increases?

driving pressure from central veins to RA (CVP)

smaller gradient

decrease in venous return


what happens to venous return when right atrial pressure decreases?

driving pressure from central veins to RA increases (increased CVP)

larger gradient

increased venous return


mean systemic filling pressure

when vascular function curve intercepts x-axis

venous return= 0L/min

this pressure is generated as a result of fullness of circulation


what effect does an increase in blood volume have on the vascular function curve?

increase mean systemic filling pressure

shift entire curve to the right


name 3 parameters that will increase venous return.

= increase cardiac output

  1. increase blood volume
  2. decrease venous compliance 
    • aka increase venous tone
  3. decrease arteriolar resistance
    • more blood shifts to venous system


how does increased venous compliance effect the vascular function curve?

increased venous compliance→ more blood held in venous reservoir of veins→ decreased venous return

curve shifts down & to the left

decreased mean systemic filling pressure


how does decreased arteriolar resistance effect the vascular function curve?

decreased arteriolar resistance= decreased tone→ increased venous volume→ increased venous pressure→ larger gradient (from right atrial pressure)→ increased venous return

mean systemic filling pressure stays the same & maximal venous return/cardiac output is increased→ slope is more extreme


how does arteriolar constriction effect arterial & venous pressures?

increase atrial pressure

decrease venous pressure


what is the independent variable on the vascular function curve?

venous return (L/min)

however the graph is always plotted inversely, so it appears on the y axis


what is the dependent variable on the Starling curve?

starling curve= cardiac function curve

cardiac output  (L/min) is dependent

right atrial pressure is independent variable


per the  Frank-Starling relationship, how does increased right atrial pressure influence cardiac output?

increased right atrial pressure→ increase in end diastolic volume (EDV)→ increased cardiac output


What factor can shift the cardiac function curve up or down?

cardiac contractility


what methods lead to hypereffectiveness of the heart & their effect on the cardiac function curve?

  • increase sympathetic stimulation
  • increase circulating epinephrine
  • + inotropic drug

curve shifts up & left


what methods lead to hypoeffectiveness of the heart & their effect on the cardiac fucntion curve?

  • decrease sympathetic stimulation
  • loss of ventricular tissue (severe MI)
  • - inotropic drugs

curve moves down & to the right


Starling's law

heart contracts more forcefully when filled to a greater degree


what effect does increasing preload have on a pressure-volume loop?

  • increased preload= increased ventricular filling (EDV) 
    • assuming fixed contractility
  • increaseds velocity of shortening
  • increased stroke volume
  • pressure-volume loop changes
    • point B shifts up & right
    • point C moves right & slightly up
    • no change of A, D, or Vmax


how does an increase in venous return affect cadiac output?

  • increased venous return
  • increases left atrial filling
  • increases preload= left ventricular filling (EDV)
  • increases sarcomere length
  • increases force of contraction
  • increases left ventricle stroke volume
  • increases cardiac output


how does a normal heart correct increased pulmonary pressure?

increased pulmonary pressure→ increase left atrial pressure→ increases left ventricular filling (EDV/preload)→ greater contractility to eject larger blood volume

caused by right heart pumping more blood (more efficiently) than the left


what effect does increasing afterload have on a pressure-volume loop?

aka increase aortic diastolic pressure w/constant contractility

  • required greater left ventricular pressure to open aortic semilunar valve, ie more time
  • decreases time foor ventricular ejection
  • decreases stroke volume
  • decreases cardiac output & increases ESV
  • pressure-volume loop changes
    • points B & C may move slightly right
    • point A shifts right
    • point D shift up & right along ESPVR line


how is increased afterload presented clinically?

normal or low systolic aortic pressure

decreased diastolic pressure

elevated left atrial pressure (from back up of blood volume)

usually caused by aortic valve stenosis


what effect does increasing contractility have on a pressure-volume loop?

caused by increasing sympathetic innervation of the heart

  • increases slope of ESPVR line
  • increases ability of cardiac muscle to shorten during contraction
  • increases pressure @ any given EDV
  • decrease in ESV
  • increases stroke volume 
  • pressure-volume loop changes:
    • point B & C stay the same
    • point A shifts left
    • point D shifts left & on new ESPVR line
    • increase in Vmax


what is a normal cause of increased contractility?



how can a ESPVR line be determined?

ESPVR= end systolic pressure-volume relastionship

  • determine PV loops of successive decreases in preload
  • line created from joining top left corner (point D) of each PV loop over a range of preloads


what is the importance of an ESPVR line?

to describe the maximal pressure that can be developed by a ventricle at any given left ventricle volume

represents end sytolic elastance (mmHg/mL- index of myocardial contrcatility)

insensitive to changes in preload, afterload, & HR


How do the adrenergic agonists work to increase contractility?

norepinephrine & epinephrine stimulate beta1 adrenergic receptors

increase sarcoplasmic Ca2+ concentrations


what pharmacological classes work as positive inotropic agents?

adrenergic agonsit (epinephrine & norepinephrine)

cardiac glycosides (ex. digitalis)


how do the cardiac glycosides increase contractility?

inhibit Na+/K+ pump→ increases intracellular Na+→ no driving force for NCX→ intracellular calcium→ increases contractility


How does sympathetic stimulation increase force of contraction?

  • norepinephrine bind beta1 receptors of cardiomyocytes
  • activates GCPR
  • Galpha-s activates adenylate cyclase
  • increases prooduction of cAMP
  • activates protein kinase A (PKA)
  • phosphorylates targets involved in regulation of Ca2+
    • L-type Ca2+ channel→ increased flux
    • RyR enhanced Ca2+
    • phosphlamban→ release of SERCA2→ faster SR Ca2+ uptake & increased SR content of Ca2+
    • troponin I→ relaxes sarcomere quicker→ higher turn over of Ca2+ binding


How does parasympathetic stimulation affect force of contraction?

decreases force of contraction

  • ACh binds to muscarinic M2 receptors
  • activates GCPR
  • Galpha-i inhibits adenylate cyclase
  • decreases production of cAMP
  • leads to regulatory binding of PKA
  • decreased Ca2+ & slower turn around of Ca2+ on sarcomere
  • decreased force of contraction


What is the physiological mechanism of action of Ca2+ channel blockers?

  • bind to intracellular side of L-type Ca2+ channels
  • decrease amount of Ca2+ entering cell
  • reduce RyR activity
  • reduces amount of Ca2+ released by SR
  • decreased contractility of heart

negative inotropic agent


what class(es) of drugs decrease contractility of the heart?

negative inotropic agents: Ca2+ channel blockers & beta blockers


How does sympathetic stimulation influence nodal cells?

  1. norepinephrine bind beta1 receptors
    • activates GCPR
    • Galpha-s activates adenylate cyclase
    • increases prooduction of cAMP
    • activates If (funny current)→ inward Na+ current
    • increased depolarization rate of phase 4 pacemaker potential
  2. IKs increased @ + voltages & deactivates @ more -voltages→ faster (shorter time period) repol.
  3. phosphorylates L-type Ca2+ channel→ opens at more - voltages & increases Ca2+ influx→ faster upstroke in SA node→ tachycardia
  4. increase speed of conduction thru AV node


What are the resulting effects of sympathetic stimulation of nodal cells?

  • increased frequency of action potentials
  • increased propagation of APs thru heart
  • shorter duration of ventricular APs
  • greater strength of contractility
  • faster rate of ventricular relaxation→ shorter duratino of systole (contraction)


How does parasympathetic stimulation influence nodal cells?


  • inhibits adenylate cyclase
    • decreasing production of cAMP
    • decreasing If activity
    • slower depolarization rate of pacemaker potential
  • opens up IK-ACh channel
    • enhances K+ permeability of SA cells
    • hyperpolarizes membrane
    • increasing voltage amount to open L-type Ca channels
    • generation of fewer action potential/time



What are the resulting effects of parasympathetic stimulation of nodal cells?


state equation for cardiac output.

CO (L/min)= stroke volume (mL/beat) x HR (beats/min)


what happens to stroke volume if preload is increased?

stroke volume is increased

preload is point B on PV loop


what happens to stroke volume if afterload is increased?

stroke volume decreases

afterload is point D on PV loop


what happens to stroke volume if contractility is increased?

increased slope of  ESPVR line

increased stroke volume


state equation for stroke volume


EDV= point B on PV loop

true ESV= point D on PV loop


what effect does sympathetic innervation have on heart rate?

increases HR



what effect does parasympathetic innervation have on heart rate?

HR decreases



 define stroke volume

volume of blood pumped by one ventricle during one beat


define cardiac output

volume of blood pumped by one ventricle in one minute


what does ejection fraction measure?

fucntion of the left ventricle

the heart's efficiency or left ventricle health

amount of blood pumped divided by amount of blood that remains in ventricle


state equation for ejection fraction.


normal at rest= 0.55-0.65


what measure is used to determine qualification for heart transplant list?

ejection fraction of 0.15 or less

aka heart is only circulating 15% of blood in ventricle


How can afterload be extracted from PV loop?

pressure at point C


How can blood pressure be estimated from PV loop?

systolic= pressure at peak of phase III

diastolic= pressure at point C


What is stroke work and how can it be obtained?

energy required to eject blood

area w/in PV loop


define barometric pressure.

pressure= weight/force over a surface area

barometric pressure applies the stratosphere, approximately 19km of gas at sea level


what are the convective processes in O2 transportation?

ventilation: atmosphere into lung & circulation to systemic capillaries


when is diffusion utilized in O2 transport?

in the aleolar-capillary membrane & capillaries into cell and mitochondria

these are slow steps of O2 transport


Approximately how much O2 is consumed at rest?

300mL/min or 432L/day


functions of respiratory system

  • gas exchange
  • talking
  • hormonal
  • and others


requirements of alveolar-capillary membrane

large & thin

  • membrane thickness
    • thinner for faster diffusion
    • thicker so it won't break under pressure
    • 1-1.5micrometers
  • large surface area to maximize diffusion area
    • 90m2 (tennis court)
    • make it fit by forming vesicular shape
  • all need access to atmosphere & to blood flow
    • branches 23X
    • approximately 200mL in pulmonary capillaries


anatomical dead space

conducting zone

air moves thru by bulk flow, not diffusion

area from trachea down thru terminal bronchioles (16 divisions)

holds approximately 150mL of air constantly


respiratory zone

aka alevolar region

where gas exchange takes place

last 7 divisions


physiological dead space

areas of alveolar region that do not participate in gas exhange

usually due to collapse of alveola or b/c alveolae are not perfused w/blood

technically includes anatomical dead space as well, therefore can only be larger or equal to anatomical dead space


What is the normal adult lung volume after expiration?


5% to dead space volume


dead space volume

5% of lung volume at end of normal expiration

usually 150mL


Where do lung volume changes occur and what is the normal range?

only in alveolar volume

total lung volume= 1.5-7L


tidal volume


volume of breath during normal breathing

approximately 500mL: 150mL to dead space & 350mL to alveolar space AT REST

increases when not quiet breathing


how is an individual's alveolar surface area calculated?

1m2/kg body mass

average is 70-90m2


what is functional residual capacity?

gas left in the lungs after expiration

approximately 3L


functions of anatomical dead space

  • conduct air to gaseous exchange region of lungs
  • heat air to body temp (37ºC)
  • humidify air to saturation level
  • clean air
    • cilia in larger bronchioles and above
    • muscous glands in brochi
    • goblet cells in bronchioles
  • defense against microbes
    • alveolar macrophages
    • IgA & IgM



why does blood pool in the lower extremities when you stand up?

gravity & high venous compliance


How does mean arterial pressure (MAP) change upon standing?

  • initial reduction along w/VR & CO due to gravity & high venous compliance
  • restored via baroreceptor reflex
    • increases HR, contractility, & TPR
    • restoring MAP, VR, & CO


how does vascular pressure vary in the supine position?

very little in arterial (head to toe: 95-100-95) or venous (head to toe: 5-2-5) systems


how does blood pressure vary while standing?

0.78mmHg/cm from the heart

bp is reduced above the heart & increased by the same amount below the heart


what are the physical mechanism(s) that oppose blood volume pooling in the venous system?

  • one-way valves
  • respiratory pumps
  • muscle pumps


where is it normal for a negative blood pressure to be found in the body?

the venous system above the heart


how are vascular pressure changes in the standing position calculated?

distance from heart in cm x 0.78mmHg/cm= XmmHg

if in arterial system +/- depending on relative position of artery to heart from the mean arterial pressure (MAP) at the level of the heart

if in venous system +/- depending on relative position of vein to heart from right atrial pressure (RAP)


what is the purpose of the nucleus tractus solitarius?

relay station & integration center for afferent information from multiple organ systems

aides in homeostatis


How does the baroreceptor reflex work?

  • decrease in arterial bp
  • decrease in afferent firing from baroreceptors (glutaminergic)
  • reduced stimulation of NTS (nucleus tractus solitarius)
  • reduces inhibition of vasomotor center (GABAergic)
    • increases activity in bulbospinal pathway
  • decreases activation of caridoinhibitory area
  • EFFECT: increase in sympathetic & decrease in parasympathetic innervation
    • increase HR, ventricular contractility, CO, & total peripheral resistance→ normalize bp


define orthostatic hypotension w/its causes & effects

inability to restore blood pressure to normal w/change in body position

most likely due to hypovolemic causes of bleeding or dehydration, but may also be due to impaired baroreceptor reflex

may cause syncope


how is orthostatic hypotension tested for?

tilt table test



what happens to blood pressure when standing from a supine position?

  • increase in venous volume of 500mL in LEs
  • decrease in intrathoracic blood volume (20%)
  • decrease SV of 30-40%
  • decrease MAP
  • activation of baroreceptor reflex or syncope due to decreased cerebral perfusion


How does standing motionless effect BP?

  • motionless standing >5min
  • increases venous pressure in LEs
  • increases venous capillary hydrostatic P in LEs
  • increases filtration in LEs
  • decreases venous blood volume
  • decreases central venous pressure
  • decreases VR & CO
  • decreases cerebral perfusion
    • syncope


how does the skeletal muscle pump reduce increase venous return?

skeletal muscle contraction forces venous blood toward heart

venous valve prevent backflow of blood

reduces blood pooling in LEs, increases VR, reduces venous volume, & venous pressure


how does the thoracic muscle pump reduce venous pooling?

  • deep inspiration
  • decreases intrathoracic pressure
  • decreases central venous pressure & right atrial pressure
  • increases driving pressure form LEs to central venous space
  • increases venous return= decreases venous pooling


how does the body meet the increased O2 demand seen in exercise?

  • increase in blood flow to active muscles
    • SNS increases CO
    • local vasodilation per metabolic theory increases blood flow to active muscles
  • active muscles extract more O2 from blood
    • greater blood flow via more capillaries→ greater surface area for exchange
    • temperature effect on hemoglobin saturation curves


What are the effects of exercise on the cardiac cycle?

  • slow filling phase of diastole significantly reduced
    • shortened TP segment on ECG
    • 1st/most effected
  • cardiac period shortened to 330-500ms
  • reduced systolic duration
  • atrial contaction maintains EDV & SV
  • increases in ventricular & aortic pressures 


what happens to stroke volume at very high HRs?

decreases due to reduced ventricular filling time

b/c systolic and diastolic phases are significantly decreased


why does stroke volume increase during initial phases of exercise?

  • increased venous return due to increased preload
  • increased contractility causes reduced ESV


how does cardiac output increase above 15L/min?

stroke volume plateaus around 160mL/beat

so CO increases due to elevations in HR: which is caused by increased SNS activity & decreased PNS activity


what are normal/trained parameters for HR?

60-80bpm healthy adults

90-100bpm sedentary, middle aged

30s bpm for elite athletes

10W exercise program can reduce HR by 10bpm



what are normal/trained parameters for SV?

  • untrained: 60-70mL/beat @ rest & 110-130mL/beat exercising
  • elite athletes: 90-130mL/beat @ rest & 150-220mL/beat exercising
    • increased filling→ EDV
    • greater contractility→ increased ejection fraction→ reduced ESV


what are the major effects of long term aerobic conditioning?

  1. reduces resting HR (increased vagal tone)
  2. physiological hypertrophy (SV)
  3. stimulates angiogenesis to exercising skeletal & heart muscle


How does physical activity affect total peripheral resistance?

  • increases sympathetic activity
    • increases CO
      • increases mean arterial pressure
    • induces vasoconstriction
      • increases TPR
  • locally causes massive vasodilation (active muscles)
    • GREATLY reduces TPR

Overall recution in total peripheral resistance


list typical pressure ranges in the heart chambers.

  • right atrium: -4 to 4mmHg
  • right ventricle: 25/0mmHg
  • pulmonary artery: 25/8mmHg
  • left atrium: 6-12mmHg
  • left vetricle: 120/0mmHg
  • aortic artery: 120/80mmHg


what is the physiological origin of S1?

occurs at closing of mitral & tricuspid valves

at the beginning of systole

produced by sudden stretching & subsequent vibration of compliant valves, surrounding connective tissue, & vessels

not by actual valve closure

**timed with upstroke of carotid pulse & beginning of ventricular contraction**


what is the physiological origin of S2?

occurs at closing of pulmonic & aortic semiluniar valves

at the beginning of diastole

produced by sudden stretching & subsequent vibration of compliant valves, surrounding connective tissue, & vessels

not by actual valve closure


what is the physiological origin of S3?

rapid ventricular filling

low pitch sound

most likely heard in apex of the heart or mitral area

diastolic heart sound after S2

normal finding in children, thin adults, thin adults & pregnanct women→ 1st 3 due to thin chest wall



what is the pathological origin of S3?

overfilling of ventricle during rapid ventricular filling phase

ex. aortic or mitral valve regurgitation


what is the physiological origin of S4?


this is a pathologic sound only


what is the pathological origin of S4?

corresponds to atrial contraction

heard late in diastole jsut before S1

vibrations caused by blood on low compliance ventricular walls

best heard over mitral valve area (apex of heart)

ex. aortic stenosis, ventriular hypertrophy due to chronic HTN


identify auscultation points of heart sounds.

all physicians take money

  • aortic valve sounds→ right parasternal 2nd intercostal space
  • pulmonic valve sounds→ left parasternal 2nd intercostal space
  • tricuspid valve sounds→ left parasternal 4th intercostal space (sometimes 3rd or 5th)
  • mitral valve sounds→ left midclavicular 5th intercostal space (apex of heart)


what is the physiological origin of S1 splitting?

left ventricle begins contraction slightly before right

mitral valve closes slightly before right

usually too narrow to hear splitting, but can be completely normal


what is the pathological origin of S1 splitting?

asynchrony of electrical system

ex. bundle branch block

cannot tell from S1 which valve is closing first


what is the physiological origin of S2 splitting?


  • decreased intrathoracic pressure
  • increases venous return & RV filling (RVEDV)
  • delays closure of pulmonic valve


what is the pathological origin of S2 splitting?

not heard during inspiration

may occur from conduction abnormalities, congenital defect, or conditions that delay RV emptying

ex. right bundle branch block/ atrial septal defect/ pulmonic stenosis


how are murmurs produced?

turbulent flow of blood

blood flow down large pressure gradient through narrow opening

categorized as systolic or diastolic depending on when they are heard


Causes of isolated systolic heart murmur.

ASS= aortic (or pulmonic) stenosis creates systolic murmur

  • aortic stenosis
    • larger than normal difference in pressures between aorta & LV (LV higher to open valve)
    • sound generated as blood is forced thru narrowed aortic valve
  • mitral regurgitation
    • blood under high pressure from LV flows thru narrow mitral valve back into LA
  • pulmonic valve stenosis
  • tricuspid valve regurgitation


when is a systolic murmur heard relative to the other heart sounds?

between S1 & S2


What would cause a S1-ssssss-split S2 heart sound and why?

atrial septal defect

murmur best heard over pulmonic area

  • LA pressure exceeds RA pressure→ blood flows L to R
  • increased RV EDV
  • produces prominent murmur thru pulmonic semilumar valve ejecting excess blood
  • delayed pulmonic closure creates split S2
    • not during inspiration due to linked atria= no net pressure change


What would cause a S1-ssssssss-split S2 heart sound and why?

ventricular septal defect

murmur best heard over tricuspid area

holosystolic: will be heard from S1 into S2

  • LA pressure exceeds RA pressure→ blood flows L to R throughout contraction
  • pressure between ventricles is not sufficient to generate audible flow during diastole
  • RV sufferes volume overload→ delayed pulmonic closure→ split S2


what can develop if a ventricular defect goes untreated?

irreversible pulmonary HTN

RV hypertrophy

Eisenmenger syndrome: RV hypertrophy exceeds LV muscle mass to reverse ventricular shut→ blood flows right to left during systole


Causes of isolated diastolic murmur.

  • aortic regurgitation
    • produced by higher pressure blood back flowing thru narrow aortic valve to low pressure ventricle
  • mitral stenosis
    • larger than normal pressure difference between LA & LV (LA higher to open valve)
    • ventricular filling occurs thru narrowed mitral valve
  • pulmonic regurgitation
  • tricuspid stenosis


when is a diastolic murmur heard relative to the other heart sounds?

between S2 & S1

S1- S2- ssssss-S1


What are the causes & effects of concentric hypertrophy?

  • definition: thickened ventricular wall & unchanged or reduced ventricular chamber diameter
    • thickening of sarcomere
  • causes: increased afterload (pressure overload)
    • chronic HTN
    • aortic valve stenosis
  • effects: decreased ventricular compliance→ S4 heart sound
    • heart failure


what are the causes & effects of eccentric hypertrophy?

aka dilated hypertrophy

  • definition: increased ventricular chamber diameter w/or w/o heart wall thickening
    • sarcomeres lengthen
    • reversible
    • may produce S3 (phys. or path. origin)
  • causes: volume overload (increased preload)
    • exercise training
    • mitral regurgitation
    • aortic regurgitation
  • effects: stress on heart→ heart failure 


How does aortic valve stenosis affect the PV loop?

  • narrowed aortic valve
  • high outflow resistance/increase in increased afterload
    • point C & D shift up 
  • impaired left ventricualr emptying- increased ESV
    • points A & D (along ESPVR line) shift R
  • decreased SV
    • phase I is shorter


How does pulmonic valve stenosis affect the PV loop?

increased apparent afterload→ rise in points C & D

decreased SV→ shortened phase I

increased ESV→ points A & D shift right


how does mitral valve stenosis affect the PV loop?

decreased preload (EDV)→ points B & C shift left

decreases stroke volume→ shortened phase I & III

decreases afterload→ lower peak of phase III, points C & D shift down


how does tricuspid valve stenosis affect the PV loop?

decreased preload (EDV)→ points B & C shift left

decreases stroke volume→ shortened phase I & III

decreases afterload→ lower peak of phase III, points C & D shift down


how doe aortic valve regurgitation affect the PV loop?

increases preload (EDV)→ points B & C shift right

increases stroke volume→ lengthened phase I & III

eccentric hypertrophy→ increased compliance

regurgitation backflow→ all points become curves; A/D & B/C volumes are no longer equal


how does pulmonic valve regurgitation affect the PV loop?

increases preload (EDV)→ points B & C shift right

increases stroke volume→ lengthened phase I & III

eccentric hypertrophy→ increased compliance

regurgitation backflow→ all points become curves; A/D & B/C volumes are no longer equal


how does mitral vavle regurgitation affect the PV loop?

increases preload (EDV)→ points B & C shift R

decreased afterload→ lower peak of phase III; points C & D shift down

 blood backflow→ decreases ESV→ points A & D shift left

increases total SV, but decreases effective SV

abberant flow causes curvature of all points


what type of murmur does aortic stenosis create?


between S1 & S2


what type of murmur does pulmonic stenosis create?


between S1 & S2


what type of murmur does aortic regurgitation create?


between S2 & S1


what type of murmur does pulmonic regurgitation create?


between S2 and S1


what type of murmur does tricuspid stenosis create?


between S2 & S1


what type of murmur does mitral valve stenosis create?


between S2 & S1


what type of murmur does tricuspid valve regurgitation create?


between S1 & S2


what type of murmur does mitral valve regurgitation create?


between S1 & S2


why is parallel vessel organization advantageous over series organization?

series organization means that all vessels have the same blood flow (L/min)

parallel enables independently regulated blood flow to each organ or region→ adaptability to different conditions


what are the parameters that affect hemodynamics?

  1. blood vessel diameter: capillaries/vena cava
  2. mean blood flow velocity: capillaries/aorta
  3. total cross-sectional area: aorta/capillaries
  4. blood volume distribution: arterioles/venous branches
  5. total peripheral resistance/systemic vascular resistance: venous branches/arterioles
  6. mean blood pressure: vena cava/aorta


define transmural pressure.

pressure measured w/blood pressure cuff


Pi= pressure stretching the vessel

Po= pressure compressing the vessel

influences vessel diameter

increased Pi→ increased wall tension

increased radius→ increased wall tension


LaPlace's law

bigger vessel radius→ bigger wall tension required to counter any given transmural pressure

T (wall tension)= Ptm x radius= (Pi-Po)r


which vessel have the greatest wall tension?



how does LaPlace's law explain aneurysm progression?

increased radius→ requires increased wall tension→ further thins & weakens wall→ increased radius, etc.


define driving pressure.

pressure difference along length of vessel

responsible for blood flow

deltaP= P1- P2 

systemic: P1= aorta & P2= RA

pulmonary: P1= pumonary artery & P2=LA


how is pulmonary driving pressure calculated?

pulmonary vascular resistance= (mean pulmomary artery pressure - pulmonary wedge pressure) / CO


how is systemic driving pressure calculated?

effectively equal to mean arterial pressure (MAP) in systemic b/c RA pressure is so low

MAP= CO x TPR (total peripheral resistance

MAP= diastolic pressure + 1/3 (systolic - diastolic)


how is pulse pressure calculated?

PP= systolic bp - diastolic bp, in mmHg

represents force that the heart generates for each contraction


where is blood flow slowest in laminar flow?

around the edges of the vessel

parabolic shape w/fastest flow in the center

makes relationship between bp & flow proportional


how can the likelihood of turbulence be predicted for a given vessel?

Renolds number, dimensionless index of flow's tendency to become turbulent

higher #= higher likelihood of turbulence

Re= [diameter(D) x flow rate(v) x fluid density(rho)] / viscosity (eta)

therefore higher diameter, flow rate & density→ turbulence & higher viscosity→ less turbulence


Darcy's law

flow= (P1-P2)/resistance (R)

  • in systemic circulation:
    • flow= LV output= CO (L/min)
    • P1-P2= aortic pressure-RA pressure= MAP (mmHg)
    • R= total peripheral resistance (TPR) or systemic vascular resistance (SVR) (mmHg•min/L)





what determines total peripheral resistance?

Poiseuille's for laminal flow

resistance = (8 x viscosity x tube length) / (pi x radius4)

greatly reduced by increased radius


what is the difference between parallel  and series vessel arrangements in respect to total resistance?

in series, individual/partial resistances are added

in parallel, total resistance is the reciprocal of the sum of the reciprocal of teh individual resistances→ total resistance is always less than single lowest resistance & resistance of arterioles in one area does not greatly alter the total


how can cardiac output be calculated from O2 consumption?

Fick's Principle

CO = rate of O2 consumptions (mL/min) / ([arterial O2]/mL - [venous O2]/mL)

venous O2 found in RA, RV, or pulmonary artery



what is static compliance & how can it be altered?

physical property of a vessel

determined by connective/elastic tissue presence

altered by age & dz

less elastic tissue→ more compliance


what is dynamic compliance & how can it be altered?

change in vascular tone due to smooth muscle contraction

altered by sympathetic nervous system stimulation of alpha1 adrenergic receptors


Define compliance.

ability of blood vessels to expand & contract passively w/changes in pressure

disten & increase volume w/increasing transmural pressure

compliance = deltaV / delta P


how is compliance shown on a V v. P graph?

the slope of the curve

veins have high compliance at low pressure & low compliance at high pressures

arteries have low compliance at all pressures


veins & arteries have different levels of compliance, so why/how is the saphenous vein used for coronary bypass?

b/c their compliance is similar at high pressures


what is stiffness?

reciprocal of compliance

stiffness = deltaP / deltaV


what happens to the V v. P curve as compliance goes down?

shifts down & right w/loss of steepness to curve


how is blood in the venous reservoir made available?

used during exercise or hemorrhage

  • increased sympathetic activity to venous smooth muscle
  • venous smooth muscle contracts
  • increases venous tone
  • decreases venous compliance
  • blood reservoir displaced toward heart
  • increased VR & CO


where is central venous pressure measured?

in thoracic vena cava near RA


what parameters affect central venous pressure?

  • blood volume
    • if increased→ increases CVP
  • compliance
    • if increased→ decreases CVP


how is central venous pressure calculated and why is it important?

delta(CVP) = delta(V) / Cv

Cv= compliance

clinical importance: determinanat of filling pressure→ preload of RV



how does a decrease in cardiac output affect central venous pressure?

  • decrease in SV or HR
  • decreases CO
  • increases venous volume
  • increases thoracic blood volume

increases CVP


how does an increase in blood volume affect CVP?

increases venous pressure

increased CVP


how does venous constriction affect CVP?

  • decreases venous compliance
  • increases VR
  • increases thoracic blood volume

incerases CVP


how does standing from a supine position affect CVP?

shift of blood volume to thoracic venous compartment

increases CVP


how does arteriolar dilation affect CVP?

  • arteriolar dilation
  • increases blood flow from arterial to venous compartments
  • increases venous volume
  • increases thoracic venous volume

increases CVP



how does muscle contraction affect CVP?

  • muscle contraction
  • compresses veins
  • blood moved toward heart

increases CVP


how does arteriolar constriction affect CVP?

  • increase sympathetic innervation
  • arteriolar constriction
  • reduces venous blood volume

decreases CVP


what maintains blood flow during ventricular diastole?

Windkessel Effect

aortic recoil after the aortic semilunar valve closes

provides additional push to blood→ moves systemically & in coronary arteries

due to static compliance of aorta & large arteries


what parameters can affect pulse pressure?

  • SV: increases PP as it increases
    • aortic valve stenosis (decreases SV)
  • arterial compliance: decreases PP as it increases
    • arteriosclerosis


how is wedge pressure measured?

  • pulmonary artery balloon catheters (Swan-Ganz) advanced thru RA & RV into pulmonary artery
  • measure pulmonary artery pressure
  • inflate balloon
  • tip of catheter on distal side of occluding balloon measures pressure


how does wedge pressure serve as a substitute for LA pressure?

due to large compliance of pulmonary circulatory system (negligable change)



What cardiac pathologies can directly increase wedge pressure?

mitral valve stenosis or CHF 


What is the normal range for wedge pressure?



What are the Starling forces and their importance?

determine net movement of fluids across capillary wall

  • forces that move fluids out of capillaries
    • capillary hydrostatic pressure (PC)
    • intersitial colloid osmotic pressure (πi)
  • forces that move fluids into capillaries
    • interstitial hydrostatic pressure (Pi)
    • capillary colloid osmotic pressure (πC): mostly albumin


which Starling forces are usually insignificant in healthy individuals?

interstitial hydrostatic pressure & interstitial colloid pressure


how is net driving force determined & what does it mean?

net driving force = forces out - forces in

= (Pc + πi) - (Pi - πc)

  • if + → net fluid movement out of capillary→ filtration
  • if - → net fluid movement into capillary→ reabsorption

hydraulic conductivity & reflection coefficient do not change significantly in physiological conditions


why does capillary hydrostatic pressure (Pc) decrease along the length of a capillary?

decrease in resistance


since filtration is greater than reabsorption over capillary length, how does the excess return to circulation?

via lymphatic system



interstitial fluid containing proteins as consquence of altered capillary permeability

ex. insect bite



aka ultrafiltrate

interstitial fluid w/o protein

ex. peripheral edema, pulmonary edema, lymphedema


how does decreased arteriolar resistance cause edema?

  • decreased arteriolar resistance
  • increases capillary hydrostatic pressure
  • increases filtration
  • edema


how does increased venous resistance contribute to edema?

  • increased venous resistance
  • increases capillary hydrostatic pressure
  • increases filtration
  • edema


how does decreased plasma protein concentration contribute to edema?

  • decreased plasma protein concentration
  • decreases capillary colloid pressure
  • decreases reabsorption
  • edema


how does decreased lymph drainage contribute to edema?

  • decreased lymphatic drainage
  • increases interstitial hydrostatic pressure
  • edema


what type of edema is seen in right sided heart failure & why?

  •  right sided heart failure
  • backup of fluid in systemic veins & capillaries
  • increases systemic capillary hydrostatic pressure
  • increases filtration/reduces reabsorption

peripheral edema


what type of edema is seen in left sided heart failure & why?

  • left sided heart failure 
  • backup of fluid in pulmonary veins & capillaries
  • increases pulmonary capillary hydrostatic pressure
  • increases filtration/reduces reabsorption

pulmonary edema


why type of edema is seen with liver or kidney failure & why?

  • liver/kidney failure
  • reduced plasma protein production (liver) or loss in urine (kidney)
  • decreases capillary oncotic (colloi) pressure
  • reduces reabsorption

peripheral edema


what type of edema is seen with lymphatic obstruction & why?

  • lymphatic obstruction caused by  sx or radiation
  • reduced flow from interstitial tissue to lymph
  • increases interstitial hydrostatic pressure
    • from fluid accumulation in interstitium
    • peripheral edema
  • increases reabsorption, but exceeds capacity of capillary reabsorption

often unilateral, dependant on cause of lymphatic obstruction


where are the high pressure baroreceptors located?

carotid sinus

aortic arch

renal afferent arteriole

in order of sensitivity


how do baroreceptors detect bp & communicate it to the nucles tractus solitarius?

stretch sensors: increased bp→ more stretch→ increased firing rate

carotid sinus baroreceptor→ glossopharyngeal (CN IX)

aortic arch baroreceptor→ aortic depressor nerve (branch of vagus/CN X)

renal→ long term bp control via renin-angiotensin


where are the low pressure baroreceptors located?

vena cava

right atrium

pulmonary artery


what do low pressure baroreceptors monitor?

venous return

volume receptors


how do the low pressure baroreceptors work?

  • increased venous return
  • increases stretch of low pressure baroreceptors
  • increases afferent signal to nucles tractus solitarius
  • regulation of effector organs to reduce volume


when does the carotid sinus nerve fiber? 

when the rate of pressure change is maximal

firing frequency is enchanced on upstroke compared to firing frequency on downstroke at the same pressure


what range is the carotid sinus baroreceptor sensitive to?


nerve firing rate is saturated at bp 200


explain how bp is normalized when a rise in bp increases baroreceptor discharge.

  • increase in bp
  • increases baroreceptor discharge
    • via excitatory glutamate on NTS
  • nucleus tractus solitarius excites (w/glutamate) caudal ventrolateral nucleus
  • stimulates GABAergic inhibitory neurons that act on vasomotor center
  • vasomotor neurons produce effect ouput to increase HR, cardiac contractility, & vasoconstriction
    • inhibited by GABA 
    • decreases their normal effectors

NTS also excites (glutamate) neurons in cardioinhibitory center= nucleus ambiguus & dorsal motor nucleus of vagus→ increases vagal innervation→ decrease HR


what is the end result of increased baroreceptor discharge?

  • vasodilation
  • venodilation→ reduces preload
  • decreases bp→ reduces baroreceptor output
  • decreases HR→ reduces CO


if high-pressure baroreceptors are so sensitive, how does HTN exist?

baroreceptors are only effective in short-term

long-term/chronic high bp lead to a 'resetting' to higher pressure as normal→ do not signal brain that pressure is elevated


what controls bp in long-term?

renin-angiotensin-aldosterone system

the kidneys


How does the renin-angiotensin-aldosterone system work?

  • reduced bp at afferent arteriole of kidney
  • stimulates release of renin form kidney
  • renin cleaves angiotensinogen from liver in circulating blood to angiotensin I
  • lung vascular endothelium angiotensin converting enzyme cleaves angiotensin I to angiotensin II
    • constricts resistance vessels→ increases systemic vascular resistance, VR→ + MAP
    • aldosterone release from adrenal cortex→ increases sodium & fluid retention in kidneys
    • stimulates release of antidiuretic hormone from posterior pituitary→ increases fluid retention by kidneys
    • stimulates thirst center in brain


how does MAP change during exercise and why isn't it corrected by the baroreceptor reflex?

MAP increases by 15-30mmHg during exercise

baroreceptor reflex is reversible reset to operate at higher set MAP point to support higher metabolic demands

extent of reset is proportional to intensity of work


What is the valsalva maneuver?

valsalva maneuver is induced when a large breath is taken & attempts to forcibly exhale w/glottis closed for at least 10 seconds→ straining

common during defecation, heavy weightlifting, & childbirth


how can the valsalva maneuver be useful?

as a test for an intact baroreceptor reflex


how does the valsalva maneuver work?

  • Phase 1
    • high thoracic pressure→ compresses aorta
    • increases arterial bp
    • decrease HR via baroreceptor activation
  • Phase 2
    • high thoracic pressure→ reduces VR
    • decreases SV & PP
    • decreases arterial PP & MAP
    • increase sympathetic outflow
    • increase HR & peripheral vasoconstriction
      • MAP stops decreasing
  • Phase 3: stop valsalva maneuver
    • decrease to normal thoracic pressure
    • decompresses thoracic aorta
    • arterial bp falls
    • HR increases
  • Phase 4
    • increase VR→ increase EDV
    • increases CO, MAP, & PP
    • activates baroreceptor reflex to transient bradycardia


why must heart patients take care not to become constipated?

b/c straining (valsalva maneuver) can kill them

elevated cardiac work & O2 demand→ increased preload in phases 1 & 4 can lead to ischemia & heart attack


3 main causes of shock.

  1. inadequate cardiac function
  2. inappropriate vascular tone
  3. inadequate blood volume


define shock.

severe reduction in blood supply to tissues


cause of hypovolemic shock

shock due to decreased blood volume

secondary to hemorrhage, dehydration, chronic or severe diarrhea or vomiting, or burns→ decreases CVP


cause of septic shock

refers specifically to decrease tissue perfusion resulting in ischemia & organ disfunction

bacterial toxins released during infection

cytokines create large scale inflammatory response→ massive vasodilation, increases capillary permeability, decreases systemic vascular resistance, & hypotension→ reduces tissue perfusion→ tissue hypoxia

**leading cause of death in ICU**


cause of cariogenic shock

reduced CO

secondary to imparied cardiac function

ex. MI


cause of anaphylatic shock

intense allergic reaction→ vasodilator release & subsequent drop in bp→ reduced organ perfusion


define neurogenic shock & its cause

loss of vasomotor tone throughout body

caused by anesthesia, brain damage, or extreme emotional insult


how does the body compensate for hypovolemic shock?

with volume losses of 10-20% only:

  • elevation of HR, cardiac contractility, & vascular resistance
  • decreased venous compliace
  • retorse MAP
  • but​ CO may be low due to reduced SV



What happens when compensatory mechanisms reach their maximum?

decompensated shock

  • compensatory mechanisms reach their maximum
    • increasing HR & vasoconstriction
  • metabolic demands are not met
  • cellular ischemia releases vasoactive mediators causing:
    • hypotension
    • shortness of breath
    • acidosis
    • cool, pale skin
    • mental confusion



What happens when volume losses exceed 20%?

irreversible shock

  • if volume loss is >20% or decompensated shock continues w/o tx for 30 minutes
  • cannot be corrected
  • further deterioration of : circulatory, endocrine, & CNS
  • results in organ damage & death


effects of left sided HF

  • decreases CO
  • increases pulmonary volume→ pulmonary edema
  • increases pulmonary capillary hydrostatic pressure
  • can lead to right sided HF
  • displays left axis deviation


effects of right sided HF

  • decreases pulmonary volume
  • decreases L heart volumes
  • decreases CO
  • increases systemic capillary hydrostatic pressure→ peripheral edema & decreases VR
  • elevated jugular pulse pressure
  • displays right axis deviation


Other than L or R sided HF, how else can cardiogenic shock be categorized?

by when the heart disfunction occurs in cardiac cycle: systole or diastole


define systolic disfunction & possible causes

reduced ability to contract or eject blood

  • causes: 
    • reduced contractility
    • increases afterload
    • uncontrolled systemic hypertension


define diastolic dysfunction and possible causes

reduced ability to relax or fill ventricle

  • causes:
    • reduced ventricular compliance (maybe S4)
    • reduced chamber volume→ reduces EDV & SV
    • reduced preload from stenosed valve


what relates cardiac performance to overall size of an individual?

cardiac index


how is cardiac index calculated?

CI = CO / body surface area (BSA

normal CI= 2.6 - 4.2 L/min per m2

higher in men than women


what is cardiac index useful as?

if it is below 1.8L/min per m2 then pt may be in cardiogenic shock


residual volume

volume at the end of maximal exhalation

approximately 1.5L


expiratory reserve volume

air that is not exhaled during normal breathing

approximately 1.5L to bring total air left in lungs up to 3L


tidal volume

change in lung volume during normal breathing

approximately 0.5L


inspiratory reserve volume

excess volume not taken during normal breathing, but is by maximal inspiratory effort

approximately 2.5L


define capacity in relation to lung volumes.

sum of 2 or more volumes:

residual volume, expiratory reserve volume, tidal volume, inspiratory reserve volume


which lung volumes can be measured by a spirometer?

inspiratory reserve volume

tidal volume

expiratory reserve volume

but not residual volume


how is residual volume measured?

helium diluting method

  • helium (or any inert gas) added to spirometer volume
  • concentration measured prior to connection to patient
  • pt exhales w/maximlal effort
  • pt connected to spirometer
  • continual breathing until equilibrium of He is reached
  • measure new concentration



how is residual volume calculated?

Fi x Vs = Fe(Vs + VL)

  • Fi = intitial He fraction
  • Vs = spirometer volume
  • Fe = He fraction at equilibrium
  • VL = residual volume (as long as pt was connected after maximal expiration)

VL = VS [(Fi - Fe) / Fe]


inspiratory capacity

sum of tidal volume & inspiratory reserve volume


functional residual capacity

sum of residual volume & expiratory volume


vital capacity

sum of expiratory reserve volume, tidal volume, & inspiratory reserve volume

largest breath that can be taken


total lung capacity

sum of all lung volumes



what effect does aging have on the lung volumes?

residual volume inceases

total lung volume increases but not as musch as residual

therefore overall vital capacity decreases with age


what are some dz that reduce vital capacity?

  • skeletal: kyphoscoliosis
  • weak respiratory muscles
    • myopathies
    • poliomyelitis
    • myasthenia gravis
  • lung dz
    • diffuse pulmonary infiltration
    • pulmonary fibrosis
    • large pleural effusion
    • collapsed lobe/lung
    • pulmonary edema
  • obstruction
    • asthma
    • chronic bronchitis
    • emphysema
    • bronchiestasis


how do obstructive lung dz affect residual volume, total lung volume and their relation to each other?

greatly increase RV

increase TLV

RV/TLV is increased



how do restrictive lung dz affect residual volume, total lung volume and their relation to each other?

decreases RV

decreases TLC

volumes are decreased proportionally→ normal RV/TLC


how is alveolar compliance calculated?

compliance (C) = (delta V) / change in transmural pressure (dPtm)


what are the 2 methods of creating a positive transmural pressure?

increasing inside pressure (Pi)

decreasing outside pressure (Po)

both cause volume expansion


what does the volume v Ptm curve represent?



As volume increases, compliance....



how is lung compliance calculated?

CL = (delta V) / (PA - Ppl)

PA = alveolar pressure

Ppl = pleural pressure


how is chest wall compliance calculated?

Ccw = (delta V) / (Ppl - PB)

Ppl = pleural pressure

Pb​ = body surface pressure


how is total respiratory system compliance calculated?

CRS = (delta V) / (PA - Pb)

PA = alveolar pressure

Pb = body surface pressure


how are lung, chest wall, and respiratory system compliance related to each other?

1/CRS = 1/CL + 1/CCW


when is respiratory system compliance at its lowest?

at total lung capacity & at residual lung volume


when is respiratory system compliance at its highest?

near the functional residual capacity (FRC)


define resting volume of respiratory system

lung volume at which transmural pressure of the respiratory system is zero

lung volume when lung recoil force is equal to chest wall recoil force (b/c they pull in opposite directions)


Is expiration or inspiration an active process?


but expiration can be when it goes below FRC


when is lung compliance at its highest?

at volume close to 0


when is lung compliance lowest?

at total lung capacity


where is resting volume of the lung found?

lung volume at which transmural pressure for lung is zero

PA - Ppl = 0


when is chest wall compliance at its lowest?

at residual volume only

there is no decrease in compliance near total lung capacity


where is resting volume of the chest wall found?

lung volume at which transmural pressure for chest wall is zero

Ppl - Pb = 0

approximately 60% of total lung capacity


what type of pathology makes lungs more compliant?

obstructive dz

ex. emphysema, COPD, chronic bronchitis, asthma

volume-pressure curve shifts left & up

expiration is difficult


what type of pathology makes lungs less compliant?

restrictive dz

ex. lung fibrosis

volume-pressure curve shifts to the right & down

inspiration is difficult


when is more muscle work needed for inspiration?

in restrictive dz

ex. lung fibrosis


when is more muscle work needed for exhalation?

obstructive dz

ex. emphysema


factors that influence compliance

  • elasticity of tissue
  • principle of interdependence of alveoli
  • surface tension
  • surfactant


what is responsible for the elastic recoil of the lungs?

# & geometrical organization of elastin & collagen fibers


explain the principle of interdependence of alveoli.

an alveolus cannot change its volume w/o affect surrounding alveoli

as one increases, compliance of surrounding decreases→ increasing volume of surrounding alveoli


why does surface tension act to decrease lung compliance?

b/c its works to reduce surface area for a given volume of a different medium

lungs are mostly water, which is different than air

occurs at air-liquid interface

behaves functionally like lung recoil force


LaPlace law

P = 2(ST/r)

ST= surface tension

r= radius


following Laplace's law, why dont' smaller alveoli collapse?

principle of interdependence of alveoli

surfactant reduces surface tension→ reduces pressure


what are the effects of surfactant?

  • decreases surface tension→ increased compliance
  • minimizes fluid accumulation in alveoli
  • keeps alveolar size relatively uniform during respiratory cycle→ equalizes ventilation amond alveoli


how does surfactant reduce surface tension?

  • replaces surface water molecules
  • hydrophilic head faces water surface of alveoli
  • hydrophobic tail strongly repels water & points toward air
    • also prevents surfactant from diving into water 
  • reduces air-water interface→ greatly reduces surface tension


how does surfactant insufficiency affect lung elasticity & compliance?

increases lung elastic recoil

2-fold decrease in lung compliance


how does surfactant keep alveolar size relatively uniform during the respiratory cycle?

as an avleoli expands, reduction in surfactant density puts a brake on further expansion

thus rerouting gas to another surrounding alveolus

equalizes ventilation among alveoli


how is surfactant cleared?

degraded by macrophages

recycled or destroyed by type II alveolar cells


what is the normal FRC?

functional respiratory capacity



why is pleural pressure negative at FRC?

b/c lung & chest wall are recoiling in opposite directions


how does pleural pressure change throughout the respiratory cycle?

  • end expiration (@FRC): -5
  • during inspiration: -8 
    • external intercostal muscles & diaphragm contraction
  • end-inspiration: -10
    • further decreases bc inspiratory muscles are still contracted
  • during expiration: -8
    • muscles relax

pressure given in cmH2O


how does alveolar pressure change throughout respiratory cycle?

  • end-expiration (@FRC): 0
  • during inspiration: -2
    • pressure difference from pressure on body surface (0) is driving force for air to enter lungs
  • end-inspiration: 0 
  • during expiration: +2 
    • lung recoil force creates + pressure in alveoli

pressures in cmH2O


what are the effects of diaphragm contractions during inspiration?

  • decreases in Ppl
    • negative PA→ creates driving force from atmosphere into lung
    • increases Ptm→ further lung distension, covering higher volume


define air flow.

V (dot on top)

air volume passing thru airway in a unit of time


what is the driving force for air flow?

pressure difference between both end of airway

expiration→ PA - Pao; where ao is airway opening

inspiration→ Pao - PA


what device is used to measure air flow?



How does the Hagen-Poiseuille law define air way resistance?

Raw = (PA - Pao) / V•


why is the Hagen-Poiseuille equation for resistance not calculable?

b/c alveolar pressure is nearly impossible to measure


How can airway  resistance be realistically calculated?

Raw = (8 x eta x L) / (π x r4)

eta=viscosity of medium→ ignored b/c air's viscosity if negligable

L= length of airway→ ignored b/c relatively constant

r= airway radius


what is the only influencing factor of airway resistance?

radius of airway

small changes cause a huge effect on resistance due to the power of 4


where is total diameter of the airway largest?

beyond the 16th generation in the respiratory zone

this also means that this is the location w/the lowest resistance


why is airway resistance a poor test for a peripheral lung obstruction?

80% of resistance is in the upper airway

branching of lower airway creates overall decrease in airway resistance, but individual bronchioles or alveolar ducts are too small to cause a change in overall resistance


5 factors influencing airway resistance

  1. density & viscosity of inspired gas
  2. Partial pressure of CO2
  3. changes in sympathetic & parasympathetic innervation
  4. agents: histamine, acetylcholine, thromboxane A2, prostaglandin F2, & leukotrienes LTB4, C4, and D4
    • ​​all bronchoconstrictors
  5. lung volume


how does respiratory air density or viscosity affect airway resistance?

directly proportional

density changes w/altitude 

viscosity changed by changing composition of inhaled air: used to replace N2 w/He

 so as they decrease so does airway resistance, or vice versa


how does the CO2 partial pressure affect airway resistance?


decreased airway PCO2→ bronchoconstriction→ increases Raw

important for regional distribution of ventilation: as one region becomes hyperventilated & PCO2 decreases→ airway resistance of that region increases→ diverting ventilation to hypoventilated areas


what effect does sympathetic innervation have on airway resistance?

sympathetic innervation→ bronchodilation via beta-receptors on smooth muscle


as the recoil force increases, compliance...



why does airway resistance decrease with increasing volume?

lung recoil is distending pressure keeping middle & small airway open

lung recoil increases w/increasing lung volume→ increases airway distending pressure→ airway diameter increases→ resistance decreases


why do emphysema paitents breathe in twice?

once to increase lung volume to decrease the airway resistance

second time to breath for ventilation since reduced resistance makes it easier to breathe


what tests allow physicians to be able to observe changes in airway resistance or respiratory system capacity?

  • forced expiratory vital capacity
  • spirograms
  • flow volume loops
  • peak expiratory flow rate


how is forced expiratory vital capacity measured?

  • pt takes maximal inspiration
  • holds breath
  • exhales as hard & fast as possible
  • gives:
    • forced expiratory volume in 1 sec (FEV1)
    • forced vital capacity (FVC)
    • ratio of FEV1/FVC→ normal= 80%
    • peak expiratory flow rate


define peak expiratory flow rate.

maximum flow rate achieved during forced vital capacity manuever beginning after full inspiration & ending w/maximal expiration


what type of pathologies lead to increases or decreases in FEV1/FVC ratios?

increase→ restrictive dz

decrease→ obstructive


how does obstructive lung dz affect forced vital capacity & forced expiratory volume in 1 second?

FEV1 & FVC are reduced, but unproportionally

FEV1 is reduced much more

so FEV1/FVC is decreased

FVC is decreased slightly b/c some airways are closed during forced expiration

FEV1 decreases b/c of high airway resistance & reduced FVC


how does restrictive lung dz affect forced vital capacity & forced expiratory volume in 1 second?

FEV1 & FVC are greatly reduced due to small total lung capacity

change is proportional or nearly so→ FEV1/FVC is normal or slightly increased


what are the forces acting on or creating alveolar pressure?

lung recoil force

expiratory muscle force


what is spirogram?

plot of exhaled volume as a function of time during a single forced expiration


how are flow volume loops obtained?

  • expiratory flow is directly measured during forced expiration & plotted against lung volume
  • when different slopes of previous expired volume-time curves are calculated in units of L/sec & plotted against corresponding lung volumes


what parameters are measured by the flow volume loops?

  • peak expiratory flow rate (PEFR)
    • dependent on pt's effort
  • forced expiratory flow at 75% capacity (FEF 75)
    • 25% of vital capacity is exhaled & 75% is in lung
  • FEF 50
  • FEF 25


why is peak flow, FEF 75, 50, and 25 decreased in restrictive dz?

reduced lung volume


why is peak flow, FEF 75, 50, and 25 reduced in obstructive lung dz?

due to high resistance


what happens to peak flow and FEF 75/50/25 values when compared to total lung capacity in lung dz states?

obstructive: reduced

restrictive: normal


how does obstructive dz shift the flow-volume curve?

shifts to the left w/decreased peak flow rate

b/c increased compliance→ increased residual voume, functional residual capacity, & total lung capacity


how does restrictive dz shift the flow-volume curve?

to the right w/decreased peak flow rate

b/c all lung volumes are proportionally smaller 

peak flow rate is reduced b/c vital capacity is smaller than normal


why does restrictive dz cause a problem with inhalation?

increased recoil/decreased compliance→ less driving force for air to enter lungs


why does obstructive dz cause a problem with expiration?

increased compliance/decreased recoil force→ decreased alveloar pressure→ decreased transmural pressure along airway→ equal pressure point w/pleural pressure occurs near alveoli (no cartilage)→ airway collapses→ air is trapped, cannot be expired


how does Pco2 change from atmospheric to physiological circulation?

0 mmHg in atmosphere (low fraction)

40mmHg in alveoli & arteries

43mmHg in mixed venous bllod & metabolic tissue


how does Po2 change from atmospheric to physiological conditions?

150mmHg in atmosphere (20% of 760mmHg)

100mmHg perfused to arteries

0mmHg in metabolic tissue

inverse of Pco2



movement of fresh air from ambient to alveoli (site of gas exchange) & subsequent movement of used air back to atmosphere

responsible for refreshing alveolar gas


tidal volume is the sum of ....

dead space volume & alveolar volume

alveolar volume is portion of tidal volume entering alveoli


number of breaths taken in one minute is referred to as?

respiratory frequency FR


what is VE & how is it calculated?

total ventilation

volume of air breathed in a unit of time (usually min)

VE = FR x VT = (FR x VD) + (FR x VA)

respiratory frequncy x tidal volume


how can dead sapce volume be calculated?

where F is gas fractions & P is partial pressures


what is basal metabolic rate & its normal values?

minimal value of O2 consumption & CO2 production

250mL O2/min


what are the influencing factors of BMR?

basal metabolic rate

temperature & body size

as they increase, so does BMR

11% for each 1ºC


define Vo2 max

maximum O2 uptake

usually 10x higher than resting value

increases proportional to work load during exercise


what is the respiratory exhange ratio and how does it vary with carbon source?

respiratory exchange ratio (R; lungs) & respiratory quotient (RQ; tissue)

R = CO2 output / O2 uptake

for carbohydrates or glucose (C6H12O6), R=1 due to 1:1 ratio of carbon dioxide to oxygen in: C6H12O6 + O2→ 6CO2 + 6H2O

fats: R=0.7 & proteins: R=0.8


when does R=RQ?

only at rest


when does R not = RQ?

exercise, holding breath, crying, hypoventilation, hyperventilation, etc.


Dalton's law of partial pressures?

Ptot = P1 + P2 + P3 + .....


ideal gas law

Px x V = Mx x R x T


state the equation to calculate partial pressure of any respiratory gas if given fractional concentration.

Px = Fx (PB - PH2O)

barometric pressure (760mmHg) - water vapor pressure (47mmHg @ 37ºC & 100% humidity as found in lungs)


what factors influence inspired oxygen partial pressure?

inspired oxygen fraction (amount of O2 in supplied air)

barometric pressure


why is O2 partial pressure reduced in alveoli compared to that in the airway or outside?

b/c O2 is continually being removed & entering capillary blood


how is alveolar oxygen partial pressure calculated when O2 is constantly being removed by blood?

PA(O2) = PI(O2) - [PA(CO2) / R]

PA = alveolar partial pressure

PI = inspired partial pressure


what is normal CO2 output?

250mL CO2/min


what is normal alveolar ventilation?



how is alveolar CO2 partial pressure calculated?


alveolar ventilation equation

VA = [VCO2 / PA(CO2)] x 863


doubling of alveolar ventilation has what effect on arterial CO2 & O2 partial pressures?

CO2: reduction by 1/2

O2: increases



normal alveolar ventilation

Pa(rterial)CO2 =40mmHg



alveolar ventilation is increased

inexcess of metabolic demand

ParterialCO2 <40mmHg


causes of hyperventilation

  • ASA toxicity
  • high altitude hypoxia
  • progesterone (pregnancy)
  • anxiety
  • metabolic acidosis



alveolar ventilation is decreased

not meeting metabolic demand

ParterialCO2 >40mmHg


causes of hypoventilation

  • primary cause: barbituate overdose
  • secondary cause: compensation for metabolic acidosis



increased ventilation w/o changes in CO2 partial pressure

ex. exercise



breathing w/increase respiratory frequency


why is increased ventilation during exercise not hyperventilation?

b/c alveolar ventilation increases to keep arterial PCO2 at normal value of 40mmHg


why is there a difference between alveolar (A) and arterial (a) PO2 & what is the normal value?

caused by normal anatomical shunts (pulmonary circulation)

normal difference is 3-10mmHg


Krough's diffusion constant


d x alpha

d= diffusion coefficient

alpha= solubility


define diffusing capacity


d x alpha x (A/T)

  • d= diffusion coefficient
  • alpha= solubility
  • A= area of membrane
  • T= thickness of membrane


how is diffusing capacity calculated?

application of Fick's law for passive diffusion & rearrangement

DL = rate of passive diffusion (Vgas) / (P1 - P2)



why can't the diffusion capacity for O2 be calculated directly?

b/c pulmonary capillary O2 partial pressure changes from the entrance @ 40mmHg to 100mmHg at teh end of the capillary


what is used to estimate diffusino capacity of O2 and how?

diffusion capacity of CO


but CO is used in very small concentrations, so PCCO=0

only difference between DLCO & DLO2 is due to their respective solubilities (alpha)


how does exercise influence diffusion capacity?

diffusion capacity increases due to recruitment & distension of pulmonary capillaries

better matching of blood flow & ventilation (greater efficiency)


how does body position influence diffusion capacity?

diffusion rate is increased in supine position v. upright

due to increased pulmonary capillary volume & more even distribution of pulmonary blood flow


how does body size influence diffusing capacity?

increases proportionally due to increased surface area that comes w/increased body size


what pathological factors can reduce diffusing capacity?

  • increased thickness, ex. pulmonary edema
  • decreased surface area
  • decreased capillary volume

seen in both obstructive & restrictive pulmonary dz, as well as LV HF & pneumonia


why does the amount of blood entering the pulmonary capillary decrease along its length?

decrease in driving force as the partial pressure reach equilibrium


how fast does gas/blood equilibrium usually take in the pulmonary capillaries?

1/4 to 1/3 of a second

but blood transit time in the capillary is on average 1 second


define diffusion limitation.

incomplete equilibriation of O2 partial pressure between alveolar gas & capillary blood

arterial PO2 remains below alveolar PO2, creating an alveolar-arterial PO2 difference


why is there no diffusion limitation on CO2?

b/c CO2 diffusing capacity is 20x higher than that of O2


when is diffusion limitation seen during exercise?

not at all in healthy subjects at sea level

CO increases much more than pulmonary capillary volume increases→ shortening blood transit time thru lung capillaries

will be seen at high altitudes or exercise of dz individuals


what are the direct causes of diffusion limitation? 

low diffusing capacity

caused by decreased alveolar surface area or increased thickess of air-blood barrier


define perfusion limitation.

limitation of gas exhange by the rate of blood flow

O2 diffusion into after equilibrium until 1 second transit time is complete


why is CO the ideal gas for measuring diffusing capacity?

limited almost entirely by diffusing properties

b/c partial pressure in capillary blood is very low due to rapid combination w/hemoglobin

thus biggest influencing factors are air-blood barrier thickness & surface area



pulmonary vascular resistance is ___ times less than total peripheral resistance.


 as displayed by low driving pressure difference from R ventricle to left atrium 


since pulmonary intravascular pressure is low, blood flow is strongly affected by?

hydrostatic (gravity) forces & perivascular pressures


how does perivascular pressure affect large extra pulmonary vessels?

  • lie in mediastinum
  • mediastinum pressure=pleural pressure= -
  • - pressure pulls vessels open
  • during inspiration, mediastinum pressure is more -
  • greater vessel dilation


how does perivascular pressure affect the pulmonary arteries & veins?

surrounded by lung tissue

same as pleural pressure→ pulled open by - pressure→ dilated by further negative pressure during inspiration


how does perivascular pressure affect alveolar capillaries?

lie w/in alveolar wall→ surrounded by alveolar pressure

compressed during inspiration when alveoli are full


how is PVR reduced?

either widening of already perfused vessels or opening of closed vessels

both occur w/increased CO

perfusion is increased 3-6x resting levels w/maximal 2x in pulmonary artery


when is pulmonary vascular resistance lowest?

at functional residual capacity of the lungs

b/c both alveolar & extaalveolar vessels are in their relaxed states


how does increased lung volume affect pulmonary vascular resistance?

increases alveolar resistance as they are compressed

decreases & dilates extraalveolar vessels (greater lung volume means more negative perivascular pressure)

there for PVR is increased


how does decreased lung volume affect pulmonary vascular resistance?

alveolar capillaries decrease in resistance

but extraalveolar vessels increase steeply in resistance

therefore PVR increases


how does the body respond to regional alveolar hypoxia?

  • inhibit Kv channels
  • depolarizes smooth muscle
  • open Ca2+ channels
  • alveolar smooth muscle contracts: vasoconstriction

decreased perfusion to hypoxia alveoli & blood diverted to physiologically acitive alveoli


what can augment pulmonary vessel constriction during regional hypoxia?

increased PCO2


hypoxic vasoconstriction in the lungs is due to?

decrease PO2 in the alveolar gas, not the blood


what are the long term effects of global pulmonary hypoxia?

pulmonary hypertension from global pulmonary vasoconstriction all the time

& eventaully right-sided heart failure


what is a possible cause of HAPE?

high altitude pulmonary edema

greater hypoxic vasoconstriction response causing pulmonary hypertension


how does NO affect PVR?

reduces PVR

one similarity to the systemic system


how does teh autonomic nervous system affect PVR?

it doesn't


how does pulmonary artery perfusion vary throughout the lungs in the upright position?

  • top: Palveolar>Ppulmonary artery>Ppulmonary vein→ compressed & no perfusion
  • middle: Ppulmonary artery>Palveolar>Ppulmonary vein→ compressed near end of pulmonary capillary & reduced perfusion
  • bases: Ppulmonary artery>Ppulmonary vein>Palveolar→ permanently prefused

perfusion increases from peak to base


how does exercise affect lung perfusion in the upright position?

exercise increases pulmonary artery pressure & reduces the inequality of blood perfusion in the lungs


What are the anatomically normal shunts?

  1. bronchial veins (deoxygenated blood from lung tissue) drains into oxygenated blood in pulmonary veins to the L atrium
  2. Thebesian veins: coronary venous (deoxygenated) blood draining into L atrium & ventricle

only 1-2% total CO

contribute equally to VA/Q mismatch for normal alveolar-arterial PO2 difference (3-10mmHg)


what are the methods of oxygen transport in blood?

dissolved & chemically bound to hemoglobin


how can the concentration of dissolved oxygen in blood be calculated?

[O2] = solubility of O2 x partial pressure of O2

0.003mL O2/100mL blood for each mmHg partial pressure of O2

thus in normal conditions: 0.003mL O2/100mL blood x 100mmHg PO2 = 3mL O2/1L blood x CO (5L/min) = 15mL O2/min

whereas normal O2 consumption is 300mL O2/min


define O2 capacity

maximum amount of O2 that can be combined w/Hb


what factor(s) is O2 capacity dependent upon?

only Hb concentration

1gm Hb binds 1.34mL O2

normal blood has approximately 15gm Hb/100mL→ 20.1mL O2/100mL


what is the driving force for diffusion of oxygen into cells?

dissolved O2 partial pressure from blood to cells


If diffusion of oxygen to cells depends on O2 partial pressure then how does Hb carried O2 participate?

  • dissolved O2 leaves blood for tissue
  • lowers partial pressure of O2 in blood
  • hemoglobin releases O2 to create equilibrium of partial pressures & further diffusion


why is average O2 saturation of Hb 75% in mixed venous blood?

  1. amount of O2 delivered to different organs varies
  2. the body always works w/reserve capacity


what is P50 used for?

P50 =O2 saturation of Hb is 50%

used as a measure for affinity of hemoglobin for O2


what are the advantages of the O2 dissociation curve?

  • upper flat portion: even if alveolar oxygen partial pressure falls slightly (dz or altitude)→ loading blood w/O2 only mildly affected
  • steep lower portion: peripheral tissues can withdrawl large amount of O2→ only small drop in capillary oxygen partial pressure

assists diffusion of O2 into tissue


how does a decrease in Hb affect O2 saturation & concentration?

reduce O2 concentration

no change in O2 saturation b/c this is dependent on Hb


how does a decrease in oxygen partial pressure affect O2 saturation & concentration?

both would be lowered


what factors increase Hb affinity for O2?

increased pH or decrease in CO2 partial pressure

pH makes a larger difference, but at CO2 concentration affects pH these factors are never isolated in reality


why does low pH reduce Hb affinity for oxygen?

low pH = high [H+]

H+ reversibly binds to imidzole group of amino acid histadine→ conformational change in Hb that decreases affinity for O2

Bohr Effect


how does high CO2 partial pressure affect Hb affinity for O2?

lowers the affinity via:

  1. CO2 binds N-terminus of alpha & beta chains of Hb
  2. causes increase in H+ ions→ decreases O2​ affinity


how does an increase in CO2 partial pressure aid in oxygen delivery?

  • CO2 is made & released to blood stream from tissues
  • increased CO2 partial pressure
  • decreases Hb affinity for O2
  • O2 freely dissolved in blood for diffusion into tissue


where can a double Bohr effect been found?

mother/fetal blood system


how does temperature affect O2 affinity and why is it advantageous or disadventageous?

affinity decreases w/increasing temperature

advantageous b/c temp rises during exercise→ Hb affinity for O2 decreases→ releasing more O2 to tissue when demand is highest


how does 2,3-BPG alter Hb affinity for O2?


reversibly binds beta chains of hemoglobin

increases in 2,3-BPG decrease affinity

helpful in chronic hypoxia (high altitude or lung dz) to unload O2 to peripheral tissue


how does CO interfere w/O2 transport?

  • b/c CO & O2 bind the same site on Hb
    • CO binds w/240x the affinity of O2
  • CO binding to Hb causes an increase O2 affinity→ inhibiting unloading to peripheral tissue


how does tx w/hyperbaric O2 work?

hyperbaric O2 = high O2 partial pressure & would drive CO off O2 binding sites


how is methemoglobin corrected?

methemoglobin has Fe3+ instead of Fe2+

plasma methemoglobin reductase can convert back to normal


Name the forms of CO2 in blood in order of percentages.



dissolved CO2


why is dissolved CO2 considered to play a significant role in its transport?

10% transported in this form

20x more soluble than O2

0.067mL CO2/dL blood per mmHg


where is the majority of bicarbonate formed?

in erythrocytes via carbonic anhydrase


what happens as HCO3- & H+ levels get too high inside the erythrocte?

H+ is buffered by Hb

HCO3- is transported into plasma via exchange protein w/Cl-


what is the Haldane effect?

unloading of O2 in peripheral capillaries facilitates loading of CO2, where oxygenation in the lung has the opposite effect

O2 binding of Hb causes decrease in H+ & CO2 binding of Hb


how are the carbamino compounds formed?

CO2 binds to terminal amino groups in blood proteins

most importantly globin of Hb


how does the CO2 dissociation curve compare to that of oxygen?

  • much steeper
  • not undergo saturation (doesn't flatten at top)
    • no maximal value for chemically bound CO2
    • CO2 concentration will always increase along w/ increase CO2 partial pressure


what factor(s) can decrease CO2 concentrations?

increased temperature

addition or increase in [H+]→ drives H+ + HCO3- ⇒ H2O + CO2 equation to the right


Bohr Effect

increases in CO2 cause an increase in H+ that binds Hb & decreases Hb affinity for O2


what are the types of tissue hypoxia?

  • stagnant: low blood flow caused by HF or vascular dz
  • anemic: reduced Hb, but Po2 is normal
  • histotoxic: inability of cells to uptake or use O2 caused by poisons like CN or HS
  • arterial hypoxia: O2 delivery to tissue is decreased by reduction in arterial O2 saturation


what are the types of arterial hypoxia?

aka hypoxemia (ParterialO2 is low)

  • low inspired PO2: high altitude 
  • diffusion limitation
  • hypoventilation
  • alveolar ventilation/perfusion mismatch
  • R to L venous shunt


what types of hypoxia display normal alveolar O2 partial pressure?

  • diffusion limited
  • V/Q mismatch
  • R→L venous shunt


what types of hypoxia have reduced values of both alveolar & arterial oxygen partial pressures?

low inspired oxygen & hypoventilation


what types of hypoxia have an increased alveolar-arterial PO2 difference?

diffusion limited

V/Q mismatch

R to L venous shunt


what can cause diffusion limited hypoxia?

severe lung damage


pulmonary edema


other than arterial hypoxia, what else does hypoventilation cause?

arterial hypercapnia


what drives the correction of hypoventilation?



why is less ventilation distributed to the apex of the lung in an upright position?

weight of lung stretches alveoli

increases volume & decreases compliance

making it more difficult to achieve change in transmural pressure


how is lung ventilation distributed throughout the lung in the upright position?

lowest at peak & increase toward base

gradient is much less prominent than that of blood perfusion



ratio of alveolar ventilation to blood perfusion

highest at apex & decreases toward base


what is the V/Q status in hyperventilated regions? hypoventilated regions?

V/Q ratio is higher in hyerpventilated & lower in hypoventilated


blood from which area of the lung have the highest PO2?

the upper regions/apex


what is an increased alveolar-arterial PO2 pressure difference a sign of?

decreased efficiency in pulmonary gas exhange


why is arterial-alveolar PCO2 difference caused by V/Q mismatch extremely small & ignorable?

  • slope of CO2 binding curve is so steep that increase in CO2 content in arterial blood is not reflected in a significant increase of arterial PCO2
  • arterial PCO2 is a strong stimulus for breathing→ small increase in PCO2 enhances ventilation & returns ParterialCO2 nearly to normal


when does V/Q=0?

R to L venous shunt

extreme hypoventilation scenario

alveolar region is not ventilated, but perfused w/blood


what is the V/Q in physiological dead space?

V/Q= infinity

alveolar region is ventilated, but not perfused


steps in differential diagnosis of hypoxia

  1. measure arterial PCO2
  2. measure arterial PO2 while breathing 100% O2
  3. measure diffusion capacity for CO


If arterial PCO2 > normal, it is hypoxia caused by _____.



If arterial PCO2 < normal, then hypoxia is caused by_____.

low inspired PO2 or high altitude


If arterial PCO2 is normal & arterial PO2 < 400mmHg on 100% O2, then hypoxia is caused by ________.

R to L shunt


If arterial PCO2 is normal & arterial PO2 > 400mmHg, then hypoxia is caused by __________.

diffusion limitation or V/Q mismatch


how are hypoxia caused by diffusion limitation & V/Q mismatch differentiated?

measuring CO diffusion capacity

< normal in diffusion limitation

normal levels in V/Q mismatch


explain how a pt w/bilateral paralysis of the diaphragm is able to breathe

via the use of accessory inspiratory muscles: external intercostals, trapezius, scalenes, sternocleidomastoid

will have tachypnea & show paradoxical inward movement of abdomen w/inspiration


where is the respiratory control center located?

in the medulla & pons


what dictates the effect a spinal cord injury has on breathing?

the spinal origin of the motor neuron to respiratory muscles


where does afferent information to the respiratory center come from?

irritant, mechanical, & chemical receptors

lungs, airway, pharynx, blood vessels, & higher centers


what cell groups comprise the ventral respiratory group?

rostral nucleus retrofacialis, caudal nucleus retroambiguus, & nuclues paraambiguus


why is inspiration a a progressive procress instead of a gasp?

inspiratory signal from the ventral respiratory group is a "ramp" up signal

starts weak & becomes stronger over 2 seconds, then ceases for 3 seconds


what is the main function of the VRG?

basic respiratory rhythm

cardiorespiratory coupling

sympathetic/parasympathetic coupling

bisic activity of bronchial muscle cells


what is the main function of the DRG?

dorsal respiratory group

integration of inputs form airway, lungs, & chemoreceptors

to modify breathing accordingly


where is the DRG located?

w/in the Nucleus Tractus Solitarus

termination of sensory input from vagus & glossopharyngeal nerves w/info from: peripheral chmoreceptors, baroreceptors, & lung respectors (stretch & nocioceptive)


what is the main function of the pneumotaxic center?

controls "off" switch of inspiratory ramp in VRG→ controls respiratory volume


where is the pneumotaxic center located?

in nucleus parabrachialis of upper pons


what are the main pulmonary receptors?

slowly adapting stretch receptors

rapidly adapting stretch receptors


muscle spindles


how are the slowly adapting stretch receptors activated?

lung distention (inspiration)

lack of change (holding breath)

deflation of lung below FRC


where are the slowly adapting stretch receptors?

airway smooth muscles 

innervated by large myelinated vagal fibers


Explain the Hering-Breuer reflex.

  • activation of slowly adapting stretch receptors during inflation
    • firing at high frequency
  • if inflation maintained, will adapt
    • firing at lower frequency
  • high activity inhibits further inspiration→ turns "off" inspiration & begins expiration

both inspiratory & expiratory terminating reflex



which receptors resond to irritants?

rapidly adapting stretch receptors

also respond to lung distention


why do lung transplant patients have a diminished cough reflex?

because the cough reflex is controlled by the rapidly adapting stretch receptors

that are located in airway epithelium & innervated by myelinated vagal fibers

vagal fibers connection to the DRG would be severed in a lung transplant


what effect does rapid firing of the rapidly adapting stretch receptors have?

cough reflex


gasp & bronchoconstriction


why does C-fiber activiation cause rapid shallow breathing, bronchoconstriction, & CV depression?

  • C-fibers=J-receptors are near capillaries
    • innervated by non-myelinated vagal fibers
  • activated by increases in interstitial fluid & pulmonary embolism
    • increased interstitial fluid causes:
    • increases air-blood barrier 
      • decreases ventilation more so in bases→ shallow breathing is preferable
      • bronchoconstriction to divert air to higher ventilation areas
    • decreases VR
      • CV depression


why is tidal volume & respiratory frequency low in obstructive lung dz?

gamma spindle fibers in muscle tissue respond to amount of motor activty/shortening of inspiratory muscle

in obstructive dz, fibers shorten, but lung volume changes lag behind so fibers shorten beyond normal

this causes large tidal volume which in turn causes low respiratory frquency


where is the central chemoreceptor located?

ventrolateral surface of medulla & medullary raphe


how is the central chemoreceptor stimulated?

by H+ and thus indirectly by CO2

not by hypoxia


how is the central chemoreceptor inhibited?

cold or anesthesia


what dz are cause by defects in the H+ receptors in the central chemoreceptors?

sleep apnea, panic disorder, epilepsy, migraine, sudden infant death syndrome (SIDS)


which peripheral chemoreceptors are not important?



what is the threshold for carotid body chemoreceptor firing?

PO2 of 80mmHg

although not significant activity until 65mmHg


what cell type is oxygen sensing and where are they located?

glomus or type I cells of the carotid body


explain the theory for how the glomus cells function.

  • K+ channel protein is primary oxygen sensor
  • inhibition of channel (low PO2 of high [H+])
  • depolarization of cell
  • activates voltage-gated Ca2+ channels
  • Ca2+ enters cell
  • causes release of neurotransmitter dopamine
  • stimulates nerve endings


what do carotid chemoreceptors respond to?

changes in PO2, PCO2, & [H+]


what creates a more potent stimulus for hypercapnia, acute or chronic exposure?

acute exposure

chronic hypercapnia causes reduced ventilatory repsonse to PCO2


why does acute hypoxia cause decreased ventilation while chronic hypoxia causes increased ventilation?

  • acute: decreased O2→ increase firing of peripheral chemoreceptors→ increased ventilation→ lowers alveolar PCO2 & raises alveolar PO2 & causes respiratory alkalosis→ inhibits peripheral & central chemoreceptors→ decrease in ventilation
  • chronic: pH is compensated→ no more inhibition of ventilation→ ventilation increases


what is anaerobic threshold?

point in exercise intensity when ventilation is no longer matched w/increase in CO2, causing changes in arterial PCO2, pH, & PO2

muscles produce lactic acid→increases [H+]→ stimulates peripheral & central chemoreceptors→ hyperventilation→ reduces Pco2