Download Pulmonary blood flow

Φσσιολογία πνεσμονικής κσκλουορίας
Ηρακλής Τσαγκάρης
Επίκοσρος Καθηγητής Εντατικής Θεραπείας
B’ Πανεπιστημιακή Κλινική Εντατικής Θεραπείας
Διακλινικό Ιατρείο Πνεσμονικής Υπέρτασης – Νοσοκομείο ΑΤΤΙΚΟΝ
Pulmonary Circulation
Two Circulations in the Lung
• Pulmonary Circulation.
– Arises from Right Ventricle.
– Receives 100% of blood flow.
• Bronchial Circulation.
– Arises from the aorta.
– Part of systemic circulation.
– Receives about 2% of left ventricular output.
Pulmonary circulation
• Pulmonary artery wall 1/3 as thick as aorta
• RV 1/3 as thick as LV
• All pulmonary arteries have larger lumen
– more compliant
– operate under a lower pressure
– can accommodate 2/3 of SV from RV
• Pulmonary veins shorter but similar
compliance compared to systemic veins
Total Pulmonary Blood Volume
• 450 ml (9% of total blood volume)
– reservoir function 1/2 to 2X TPBV
– shifts in volume can occur from pulmonary to
systemic or visa versa
• e.g. mitral stenosis can pulmonary volume
100%
• shifts have a greater effect on pulmonary
circulation
Systemic Bronchial Arteries
• Branches off the thoracic aorta which
supplies oxygenated blood to the
supporting tissue and airways of the lung.
(1-2% CO)
• Venous drainage is into azygous (1/2) or
pulmonary veins (1/2) (short circuit)
– drainage into pulmonary veins causes LV
output to be slightly higher (1%) than RV
output & also dumps some deoxygenated
blood into oxygenated pulmonary venous
blood
Pulmonary lymphatics
• Extensive & extends from all the
supportive tissue of lungs & courses to the
hilum & mainly into the right lymphatic duct
– remove plasma filtrate, particulate matter
absorbed from alveoli, and escaped protein
from the vascular system
– helps to maintain negative interstitial pressure
which pulls alveolar epithelium against
capillary endothelium. “respiratory membrane”
Pulmonary Circulation
• In series with the systemic circulation.
• Receives 100% of cardiac output (3.5L/min/m2).
• RBC travels through lung in 4-5 seconds.
• 280 billion capillaries, supplying 300 million
alveoli.
– Surface area for gas exchange = 50 – 100 m2
Alveolar Architecture
Alveolar Airspace
Alveolar Airspace
Functional Anatomy of the
Pulmonary Circulation
• Thin walled vessels at all levels.
• Pulmonary arteries have far less smooth
muscle in the wall than systemic arteries.
• Consequences of this anatomy- the
vessels are:
– Distensible.
– Compressible.
Pulmonary Circulation Pressures
Pulmonary Vascular Resistance
input pressure - output pressure
Vascular Resistance =
blood flow
PVR = k • mean PA pressure - left atrial pressure
cardiac output (index)
mean PA pressure - left atrial pressure = 10 mmHg
mean aorta pressure - right atrial pressure = 98 mmHg
Therefore PVR is 1/10 of SVR
Vascular Resistance is Evenly Distributed in
the Pulmonary Circulation
Reasons Why Pressures Are Different in
Pulmonary and Systemic Circulations?
• Gravity and Distance:
– Distance above or below the heart adds to, or
subtracts from, both arterial and venous pressure
– Distance between Apex and Base
Aorta
Systemic
100 mmHg
Pulmonary
Main PA
15 mmHg
Head
50 mmHg
Apex
2 mmHg
Feet
180 mmHg
Base
25 mmHg
Reasons Why Pressures Are Different in
Pulmonary and Systemic Circulations?
• Control of regional perfusion in the systemic circulation:
– Large pressure head allows alterations in local vascular resistance to
redirect blood flow to areas of increased demand (e.g. to muscles
during exercise).
– Pulmonary circulation is all performing the same job, no need to
redirect flow (exception occurs during hypoxemia).
• Consequences of pressure differences:
– Left ventricle work load is much greater than right ventricle
– Differences in wall thickness indicates differences in work load.
Influences on Pulmonary Vascular Resistance
Pulmonary vessels have:
-Little vascular smooth muscle.
-Low intravascular pressure.
-High distensiblility and compressiblility.
Vessel diameter influenced by extravascular forces:
-Gravity
-Body position
-Lung volume
-Alveolar pressures/intrapleural pressures
-Intravascular pressures
Influences of Pulmonary Vascular Resistance
•Transmural pressure = Pressure Inside – Pressure
Outside.
–Increased transmural pressure-increases vessel diameter.
–Decreased transmural pressure-decreased vessel diameter
(increase in PVR).
–Negative transmural pressure-vessel collapse.
Pi
Poutside
•Different effects of lung volume on alveolar and
extraalveolar vessels.
Effect of Transmural Pressure on Pulmonary Vessels
During Inspiration
Resistance
Length and Resistance
1/(Radius)4
Effect of Lung Volume on PVR
Pulmonary Vascular Resistance During Exercise
• During exercise cardiac output increases (e.g. 5-fold), but
with little change in mean pulmonary artery pressure
– How is this possible?
input pressure - output pressure
Vascular Resistance =
blood flow
• Pressure= Flow x Resistance
• If pressure does not change, then PVR must decrease with
increased blood flow
• Passive effect (seen in isolated lung prep)
– Recruitment: Opening of previously collapsed capillaries
– Distensibility: Increase in diameter of open capillaries.
Recruitment and Distention in Response to
Increased Pulmonary Artery Pressure
Control of Pulmonary Vascular Resistance
• Passive Influences on PVR:
Influence
Effect on PVR
Mechanism
(above
Increase
Lengthening and
Compression
(below
Increase
Compression of
Extraalveolar Vessels
Decrease
Recruitment and
Distension
Decrease in Dependent
Regions
Recruitment and
Distension
Interstitial Pressure
Increase
Compression
Positive Pressure
Ventilation
Increase
Compression and
Derecruitment
Lung Volume
FRC)
Lung Volume
FRC)
Flow, Pressure
Gravity
Regional Pulmonary Blood Flow Depends
Upon Position Relative to the Heart
Main PA
Apex
Base
15 mmHg
2 mmHg
25 mmHg
Gravity, Alveolar Pressure and Blood Flow
• Pressure in the pulmonary arterioles depends on both mean
pulmonary artery pressure and the vertical position of the vessel in
the chest, relative to the heart.
• Driving pressure (gradient) for perfusion is different in the 3 lung
zones:
– Flow in zone may be absent because there is inadequate pressure to
overcome alveolar pressure.
– Flow in zone 3 is continuous and driven by the pressure in the
pulmonary arteriole – pulmonary venous pressure.
– Flow in zone 2 may be pulsatile and driven by the pressure in the
pulmonary arteriole – alveolar pressure (collapsing the capillaries).
Gravity, Alveolar Pressure, and Blood Flow
Typically no zone 1 in
normal healthy person
Large zone 1 in
positive pressure
ventilation + PEEP
Alveolar Dead Space
Control of Pulmonary Vascular Resistance
• Active Influences on PVR:
Increase
Decrease
Sympathetic Innervation
Parasympathetic Innervation
-Adrenergic agonists
Acetylcholine
Thromboxane/PGE2
-Adrenergic Agents
Endothelin
PGE1
Angiotensin
Prostacycline
Histamine
Nitric oxide
Alveolar Hypoxemia
Bradykinin
Hypoxic Pulmonary Vasoconstriction
• Alveolar hypoxia causes active vasoconstriction at level of precapillary arteriole.
• Mechanism is not completely understood:
– Response occurs locally and does not require innervation.
– Mediators have not been identified.
– Graded response between pO2 levels of 100 down to 20 mmHg.
• Functions to reduce the mismatching of ventilation and perfusion.
• Not a strong response due to limited muscle in pulmonary
vasculature.
• General hypoxemia (high altitude or hypoventilation) can cause
extensive pulmonary artery vasoconstriction.
Hypoxic pulmonary vasoconstriction
Arterioles
30-200μm
Barrier Function of Alveolar Wall
• Capillary endothelial cells:
– permeable to water, small molecules, ions.
– barrier to proteins.
• Alveolar epithelial cells:
– more effective barrier than the endothelial
cells.
– recently found to pump both salt and water
from the alveolar space.
Starling’s Equation
Q=K[(Pc-Pi) – ( c- i)]
Q = flux out of the capillary
K = filtration coefficient
Pc and Pi = capillary and interstitial hydrostatic
pressures
c and i = capillary and interstitial osmotic
pressures
= reflection (sieving) coefficient
Pulmonary Capillary dynamics
• Starling forces (ultrafiltration)
– Capillary hydrostatic P = 7 mmHg.
– Interstitial hydrostatic P = -8 mmHg.
– Plasma colloid osmotic P = 28 mmHg.
– Interstitial colloid osmotic P = 14 mm
•
•
•
•
Filtration forces = 15 mmHg.
Reabsorption forces = 14 mmHg.
Net forces favoring filtration = 1 mmHg.
Excess fluid removed by lymphatics
Normally Starling’s Forces Provide Efficient
Protection
• Normal fluid flux from the pulmonary capillary bed is
approximately 20 ml/hr.
– recall that cardiac output through the pulmonary
capillaries at rest is ~5 l/min.
– < 0.0066% leak.
• Abnormal increase in fluid flux can result from:
– Increased hydrostatic pressure gradient (cardiogenic
pulmonary edema).
– Decreased osmotic pressure gradient (cirrhosis,
nephrotic syndrome).
– Increased protein permeability of the capillary wall
(ARDS).
Pulmonary Pressures
• Pulmonary artery pressure = 25/8
– mean = 15 mmHg
• Mean pulmonary capillary P = 7 mmHg.
• Major pulmonary veins and left atrium
– mean pressure = 2 mmHg.
Ορισμοί
Ορισμός PAH (2004)
• Μέση PAP> 25 mmHg
(> 30 mmHg during exercise)
Φσσιολογικές
τιμές
(10-15)
• PCWP<15 mmHg
(2-12)
• PVR > 3 Wood units
(2-3)
Etiologic classification of pulmonary hypertension
• MPA - PCWP = CO
*
PVR
• MPA = CO *
+
PCWP
PVR
Pulmonary Hypertension: Define Lesion
Post-Capillary PH
(PCWP>15 mmHg; PVR nl)
Respiratory
Diseases
VC
RA
RV
PA
PV
PC
Pre-capillary
PH
PCWP<15 mmHg
PVR > 3 Wu
LA
LV
LVEDP
Ao
Progression of vascular disease
Schematic Progression of PAH
Pre-symptomatic/
Compensated
Symptomatic/
Decompensating
Declining/
Decompensated
CO
Symptom Threshold
PAP
PVR
Right Heart
Dysfunction
PAP-PCW
PVR=
CO
Time
Pathways in the pathogenesis of PH
Mechanisms of InflammationMediated Remodeling
Kovacs, ERJ, 2012
Kovacs, ERJ, 2012
Kovacs, ERJ, 2012
PH due to left heart disease
Venice 2004
Dana Point 2008
The accuracy of Doppler Echocardiography
in assessing systolic PAP
Arcasoy, AJRCCM, 2003
The accuracy of Doppler Echocardiography
in assessing systolic PAP
Arcasoy, AJRCCM, 2003
΢ημεία πνεσμονικής σπέρηαζης
MDCTPA
Διάμετρος > 29 mm
PPV 97%, sens 87%, spec 89%.
ΠΡΟ΢ΟΧΗ!! Διάμεηρος κύριας
πνεσμονικής αρηηρίας < 29 mm
ΔΕΝ ΑΠΟΚΛΕΙΕΙ πιθανή παροσζία
πνεσμονικής σπέρηαζης.
Όηαν η πνεσμονική αρηηρία > 29
mm και ο λόγος διαμέηροσ
ημημαηικής αρηηρίας/ βρόγτο
είναι > 1 ζε 3 από ηοσς 4
πνεσμονικούς λοβούς, ειδικόηηηα
100% για παροσζία πνεσμονικής
σπέρηαζης.
Διάμετρος > 29 mm
Διάμετρος ΠΑ > διάμετρο
ΑΑ
Διάμετρος ΠΑ > διάμετρο ΑΑ
Πνεσμονική αρηηρία > ανιούζα
θωρακική αορηή: PPV 96%, spec
92%, ειδικά ζε αζθενείς < 50
εηών.
΢ημεία πνεσμονικής σπέρηαζης
MDCTPA
+ περικαρδιακή ζσλλογή ΚΑΚΟ προγνωζηικό
ζημείο
Pulmonary Veno-Occlusive Disease
Septal lines
Ground glass
opacities
Mediastinal
lymphadenopathy
 100% spec, 66%
sens
Resten et al. AJR 2004;183:6570
56 yo, PVOD
Pulmonary Veno-Occlusive Disease
•Vasodilators and especially prostanoids must be used with great
caution because of the high risk of pulmonary edema.
•HRCT is the investigation of choice
Galie N, Hoeper MM, Humbert M, et al.
Eur Resp J 2009; 34: 1219-1263.
Montani Det al. Medicine 2008;87:220-233
Montani D et al. Eur Resp J2009;33:189-200
A. A. Frazier et al. Radiographics 2007;27:867882
Normal
PVOD
Normal
PCH
Future in imaging
• Pathological remodeling occurs at the level of
the pulmonary resistance vessels measuring
approximately 100 μm in diameter.
• If one were able to visualize these small
vessels, recognize occlusions, and ultimately
also identify hypertrophy of the smooth muscle
cell layer, one might be able to predict the
development of pulmonary hypertension at early
stages when hemodynamics are still normal.
New CTs
• The current generation of 64-slice (and higher)
multidetector CT (MDCT) scanners allow for
better spatial (versus CMR) and temporal
(versus older scanners) resolution, shorter
scanning
times
and
breath-holds,
and
electrocardiogram (ECG)-gated acquisition for
detailed cardiac structural analysis.
Future challenges
• Accurate visualization of complex RV
anatomies by advanced imaging
techniques and precise measurement of
blood volumes and flow may obviate
invasive procedures in the future (??).
Vasoreactivity testing with
Epoprostenol
Critical pathways in cardiology
March 2012 Volume11 (1); 40-2
Arterial or upstream (Rup) and capillary-venou
or downstream component:
Rup% = 100 x (mPpa – Poccl)/(mPpa – Ppao
dPAP-PAOP
•
•
•
•
Normal value 1-2 mmHg
Abnormal level > 5mmHg
Prognostic marker >7mmHg
Precapillary PH > 10mm Hg
W
dPAP-PAOP
Isolated post capillary PH
>15mmHg
<7mmHg
Combined post and precapillary
PH
>15mmHg
>7mmHg
Terminology
Πμερμξμξπάθεια και PH: Μηςαμιζμξί
 Υπξνική αγγειξζύζπαζη
 Μείωζη ηηπ πμερμξμικήπ αγγειακήπ κξίηηπ
 Αύνηζη ηηπ καοδιακήπ παοξςήπ και ηηπ
γλξιόηηηαπ ηξρ αίμαηξπ
Χοόμια ρπξνία: Πειοαμαηικό
μξμηέλξ δημιξρογίαπ PH
Chen, JAP, 1995
Down regulation of endothelial NO synthase
Decreased release of NO
Down regulation of voltage gated K channels
Increased intracellular free Calcium and smooth muscle contraction
Neomuscularization of the arteriole, intimal
thickening and medial hypertrophy
Hypoxia induced remodeling
Stenmark, Cirk Res, 2006
Hypoxia induced remodeling
Stenmark, Cirk Res, 2006
Stenmark, Cirk Res, 2006
Upregulated/(downregulated)
Suggested classification and management
Undelying lung disease
mPAP<25mm
Hg
mPap 2535mmHg
mPAP > 35 mmHg
COPD with FEV1>60%
IPF with FVC > 70%
No gross parenchymal or airway
abnormalities on CT
No PH
No PAH
treatment
recommended
Meet criteria for PAH Meet criteria for PAH
PAH treatment
PAH treatment
guidelines may
Guidelines may apply
apply
COPD with FEV1<60%
IPF with FVC < 70%
Combined pulmonary lesions and
emphysema on CT
No PH
No PAH
treatment
recommended
PH-COPD, PH-ipf,
PH-cpfe
No data support
treatment
severePH-COPD,
PH-ipf, PH-cpfe
Refer to center for
individualized care
RCTs needed
WORLD SYMPOSIUM PH, 28 Feb 2013
Seeger W.
PAH treatment bridge
to TX