Ch. 4 Blood Flow and Metabolism
Right Ventricle  Pulmonary Artery  Terminal Bronchioles  plexus  capillaries
Pressures w/in Pulmonary BV’s

Pressures in pulmonary circulation are remarkably low

Pulmonary artery 15mm Hg (systolic – 25mmHg; diastolic –8 mmHg)

Pressure @ inlet 10 mmHg; pressure @ outlet ~100 mmHg

Pulmonary vasculature – contain very little SM o Responsible for accepting 100% of CO o Rarely concerned with directing flow – keeps Rt. Heart small

Pressures usually b/t 12 mm Hg and 8 mm Hg
Pressures around Pulmonary BV’s

Pulmonary capillaries are virtually surrounded by gas

If alveolar pressure >> capillary pressure  collapse occurs

Transmural pressure (Pin – Pout) – for capillary to NOT collapse – P
TM
>> P
A o In other words—as long as transmural pressure is positive – collapse is prevented; and if transmural pressure (w/in the cap) becomes negative – collapse will occur (( d/t pressure of alveoli on the capillary))

Both pulmonary arteries and veins increase their pressure (w/in) during inspiration o Large BV’s (i.e. pulmonary artery) – “extra-alveolar vessels” – includes arteries and veins that run through the lung parenchyma
 Caliber/diameter is greatly affected by lung volume b/c this determines the expanding pull of the parenchyma on their walls
 Very large vessels near the hilum are outside of the lung substance and are exposed to intrapleural pressure o Small BV’s (i.e. capillaries) – “alveolar vessels”
 Caliber/diameter determined by the relationship b/t alveolar pressure and pressure inside  (i.e. Transmural pressure)

Summary of Alveolar and Extra-Alveolar Vessels o Alveolar vessels are exposed to alveolar pressure and are compressed if this increases
(again, if Transmural pressure  0 and then negative; collapse occurs) o Extra-alveolar vessels are exposed to a pressure less than alveolar, and are pulled open by the radial traction of the surrounding parenchyma
Pulmonary Vascular Resistance
Vascular resistance = (input pressure – output pressure) / blood flow

Pressure drop across pulmonary vasculature ~ 10 mm Hg; therefore pulmonary vascular resistance is about 1/10 th of systemic


Pulmonary blood flow = 6 L/min

Pulmonary vascular resistance = (15-5) / 6 ~= 1.7 mm Hg/(1/L)/min

Pulmonary resistance decreases as pressure increases o Why? o 1) Recruitment: under normal conditions, some cap’s are either closed, or open – but receive little or no blood flow (i.e. apex of lung) --- as pressure rises, these vessels begin to conduct blood, thus lowering the overall resistance (i.e. in parallel)
 Chief mech. For the fall in pulm. Vascular resistance that occurs as the pulmonary artery pressure is raised from low levels o 2) distension: at higher capillary pressures, distension occurs (vasodilation)
 Predominant mechanism for the fall in pulmonary vascular resistance at relatively high vascular pressures
 Remember: a positive transmural pressure = distending pressure (i.e. how you prevent collapse of trachea on expi w/ large drop in pressure in airways)— cartilage provides the increase in transmural pressure b/t airway (pressure forcing expansion) and lungs (pressures promoting collapse) o 3) lung volume: capillaries are pulled open as the lung expands  vascular resistance is low at large lung volumes
 Also, the capillaries have a high resistance when lung volumes are low (i.e. max expi or at FRC, or RV)
 Critical opening pressure – amt. of pressure that pulmonary artery must provide for collapsed vessel’s Pressure to be equal and opp. To pleural pressure
 (i.e. restore a positive transmural(distending pressure) once a negative transmural pressure/collapse has occured

Lung Volume o EPP (equal potential pressure) or Critical opening pressure o EPP occurs where the pressure in the capillary is equal to the pressure in the alveolus o If EPP occurs within the lower airways  collapse of vessel occurs o The vessel cannot be openend until the pressure of the capillary becomes equal to or greater than the pressure w/in the alveolus  critical opening pressure (see animation) o Even if the pressure in the cap’s is not changed w/ large lung inflations (inspi), the capillaries resistance increases o Drugs that cause contraction of pulmonary vessels (i.e. Beta 2 agonist—albuterol, ach, isoproterenol) cause contraction of the SM increasing pulmonary vascular resistance
(i.e. increasing flow)
 Serotonin, histamine, norepi—potent vasoconstrictors
 Prostacyclin – potent vasodilator o Summary of Pulmonary Vascular Resistance
 It is normally very small
 Decreases on exercise b/c of recruitment and distention of capillaries
 Increases at high and low lung volumes

 Increases with alveolar hypoxia b/c of constriction of small pulmonary arteries
Measurement of Pulmonary Blood Flow

Fick principle: o The O2 consumption per minute (dot VO2) is equal to the amt. of O2 taken up by the blood in the lungs per minute o B/c the O2 concentration in the blood entering the lungs is C(line)VO2 and blood leaving is CaO2 :
 (dot)Q ((Perfusion)) = Ventilation of O2 / (Concentration of arterial O2 –
Concentration of blood entering the lungs)
 Q = V
O2
/ (C aO2
– C
VO2
)
Distribution of blood Flow


Blood flow decreases linearly from bottom to top, reaching very low perfusion values at the apex

Distribution of blood is dependent on posture and exercise

Supine position: apical zone blood flow increases, but the basal zone flow remains unchanged

Uneven blood flow is d/t hydrostatic pressure differences w/in bv’s. o Zone 1 aka Alveolar Dead Space
 P
A
> P a
> P
V
 – where pulmonary arterial pressure falls below alveolar pressure – capillary collapse (negative P
TM
)
 normally doesn’t occur b/c the pulmonary arterial pressure is sufficient to raise blood to top of the lung but may occur if arterial pressure drops (i.e.
 hemorrhage) or if alveolar pressure is raised (i.e. positive ventilation) o Zone 2
 P a
> P
A
> P v
 Pulmonary arterial pressure >> alveolar pressure
 Venous pressure << alveolar pressure
 Blood flow is determined by the difference b/t arterial and alveolar pressures o Zone 3

 P a
> P
V
> P
A
 Venous pressure exceeds alveolar pressure
 Transmural pressure is positive throughout length of tube
 Mean width increases
 Recruitment can increase blood flow in this zone o Zone 4
 Region of reduced blood flow, occurs when lung is poorly inflated
 At low lung volumes, the resistance of extra-alveolar vessels becomes important, and a reduction of regional blood flow is seen  starting at base

General Blood Flow: Periphery << Central regions
Active Control of Circulation

Importance: o Effect of directing blood flow away from hypoxic regions of the lung ( i.e. d/t obstruction) o Assist in matching V/Q ratio (i.e. ventilation to perfusion = 1/1 normally) o Occurs at high altitude

Hypoxic pulmonary Vasoconstriction – P
A
O2 is reduced

Occurs when PAO2 << 70 mm Hg (normal PA/aO2 = 100 mm Hg) o Contraction of SM in the walls of the small arterioles in the hypoxic region o Not dependent on CNS connections o Vasoconstriction is determined by: PA
O2
 Decreased PAO2  Inhibition of voltage gated K+ channels  Increased cytoplasmic Ca++  SM contraction  Increased pulmonary vascular
resistance o Fetal
 Relatively low oxygen
 High pulmonary resistance
 First Breath  removes hypoxic vasoconstriction
 Increased O2
 Decreased pulmonary vascular resistance o NO mech.
 Block NO  increase Hypoxic Vasoconstriction
 Adm. NO  reduce hypoxic vasoconstriction (20mm usually, lethal at high doses)
 NO is created from L-arginine via catalysis by eNOS
 NO activates cyclic GMP  SM relaxation
 o Pulmonary endothelial vasoconstrictors
 Endothelin-1 (ET-1)
 Thromboxane A
2
(TXA
2
)

o Other causes of vasoconstriction:
 Decreased pH (i.e. anaerobic metab.)
 Increased sympathetic activity

Hypoxic Pulmonary Vasoconstriction o Alveolar hypoxia constricts small pulmonary arteries o Probably a direct effect of the low PaO2 on vascular smooth muscle o Critical at birth in the transition from placental to air breathing o Directs blood flow away from poorly ventilated areas of the diseased lung in the adult o PAO2 of 100 mm Hg = 80 % flow (normal) o PAO2 of 50 mm Hg = 40% flow (vasoconstriction) o PAO2 of 150 mm Hg = 90% flow (i.e. adm NO)
Water Balance in the Lung

Distance b/t capillary blood from alveolar air = 0.3 µm

Fluid exchange across capillary endothelium obeys Starling’s law o Force tending to push fluid out of the capillary is hydrostatic pressure minus the hydrostatic pressure of the interstitial fluid ( P
C
– P i
) o Force tending to pull fluid in is the osmotic pressure of the proteins of the blood minus that of the proteins of the interstitial fluid (π
C
– π i
) o σ – is the effectiveness of the capillary wall in preventing the passage of proteins across it; termed reflection coefficient o K = filtration coefficient o Net fluid out = K[(P
C
– P i
) – σ (π
C
– π i
) o Capillary osmotic pressure ~ 28 mm Hg o Colloid osmotic pressure of interstitial fluid ~ 20 mm Hg o Net result: outward Pressure – causes about 20ml/hr to diffuse from capillary into interstitium

Where does the fluid go? o Fluid which leaks out into the interstitium of the alveolar wall tracks through the interstitial space to the perivascular and peribronchial space w/in the lung
 Numerous lymphatics brings this fluid to hilar lymph nodes o Interstitial edema -- Earliest form of pulmonary edema is characterized by engorgement of the peribronchial and perivascular spaces o Later stage of pulmonary edema – fluid may cross the alveolar epithelium into the alveolar spaces
 Alveoli fill w/ fluid one by one, and b/c they are unventilated  no diffusion occurs (i.e. no oxygenation & no removal of CO2) o Fluid that reaches the alveolar spaces is actively pumped out by Na+,K+, and ATPase pumps in epithelial cells o Seriousness: alveolar edema >>>> interstitial edema

Other Functions of the Pulmonary Circulation (see Ch.1 summary)

Acts as reservoir of blood

Ability to reduce pulmonary vascular resistance as its vascular pressures are raised through: recruitment and distension o Same mechanism allows lung to increase its blood volume w/ relatively small rises in pulmonary arterial or venous pressures. (i.e. change in posture from standing  supine)
 Blood then drains from legs  lung

Acts as a filter for blood o Small thrombi are removed from the circulation before they can reach the brain or other vital organs o Traps WBC’s (fx unknown)
Metabolic Functions of the Lung


See chart Ch.1 summary
Activated in lung: o Vasoconstrictors:
 Angiotensin I  angiotensin II

Angiotensin II has NO effect on the lung vasculature itself (i.e. effects systemic vasculature)

ACE located in small pits on surface of capillary endothelial cells

Inactivated in lung: o ACE o Vasodilators:
 Bradykinin (80% inactivated) o Uptake and storage of serotonin (almost completely removed) o PGE1, PGE2, PGF2α o NE o Histamine

Arachadonic acid and Metabolites released in blood o Membrane-bound phospholipid o ↓ ←Phospholipase A2 o Arachidonic Acid o Lipoxygenase→↙ ↘←Cyclooxygenase o Leukotrienes Prostaglandins, thromboxane A2

Prostaglandins are potent vasodilators and vasoconstrictors o PGE2 – relaxes patent ductus arteriosus o Also effects kallikrein-kinin clotting cascade o Asthma?

Misc: o Mast cells containing heparin in interstitium

o IgA – antibiotic defense o Synthesis of surfactant by type II pneumocytes o Leukocytes  cause of emphysema via breakdown of elastin and fibrin? o Carbohydrate metabolism (via mucopolysaccharides in mucus)