Cardiovascular Physiology VI.

50. Pulmonary circulation.32. Biology of the airways. Metabolic and endocrine functions of the lung.40. Cardiac work and metabolism. The coronary circulation.51. Skeletal muscle blood flow, the cardiovascular adaptation to work and exercise.

Ferenc Domoki, November 24 2021.

Characterization of the circulation in specific regions

Quantitative data: % of cardiac output, tissue blood flow (ml/g/min), O2-consumption etc.

Organ specific morphological features: arteries, microcirculation, veins

specifics in capillary transport

regulation of local blood flow!

Pulmonary circulation

The organ with the HIGHEST blood flow! (= CO)

Low pressure – low resistance circulatory bed!

Pulmonary circulation Systemic circulation

PA systolic pressure 24 mmHg Aorta systolic pressure 120 mmHg

PA diastolic pressure 9 mmHg Aorta diastolic pressure

80 mmHg

PA mean pressure 14 mmHg Aorta mean pressure 93 mmHg

Pulmonary capillary mean pressure

10 mmHg Systemic capillary mean pressure

25 mmHg

Left atrial pressure 6-8 mmHg Right atrial pressure 0-2 mmHg

PVR 1.5 mmHg×min/l

TPR 16 mmHg×min/l

Anatomical features

Arterial compliance is similar to venous, thus ~10% of blood volume is evenly distributed between the pulmonary arteries and veins, the capillaries contain ~80 ml of blood.

The bronchial arteries (from aorta) provide NUTRITIVE blood flow to the larger airways (1-2% of CO), physiologic shunt flow.

PVR is affected greatly by PASSIVE mechanisms due to the low pressure and large compliance values. Major aspects: 1. the force of gravity in upright humans, 2. increase of PA pressure / CO, 3. changes in lung volume.

alveolar pressure

dis

tan

ce f

rom

bas

eperfusion

The effect of gravity: vertical gradient of transmural pressure develops in standing position

pressure inpulmonary artery

pressure inpulmonary vein

No flow

Intermittentflow

Continuous flow

Fortunately in healthy people there is no Zone I flow

Bedrest is putting every lung region in Zone III. People with pulmonary infections, shock MUST stay in bed!

Effect of gravity on pulmonary circulation

3-fold gradient!

PVR decreases if blood pressure and/or CO increases, because

Due to the enormous compliance, small increases in transmural pressure lead to the dilation of extralveolar vessels

The alveolar capillary network has multiple branching (net-like, sheet like flow), so increases in flow passively opens new passageways (capillary recruitment)

Vascular resistance is affected by lung volume

Quiet, tidal breathing

Inflation of alveoli is pulling (distending) the blood vessel in the lung parenchyma (extraalveolar vessels), but the inflation will compress the septal capillaries

Optimal resistance: around the FRC volume!

It is of importance how artificial ventilation parameters are set!

Pulmonary microcirculation

VERY thin (0,3 mm!) capillaries, that are permeable to fluid

Edema entering the alveoli can be lethal!

From the Starling-forces, especially the LOW capillary hydrostatic pressure limits fluid filtration

Rich lymphatic vascularization also protects from pulmonary edema

Alveolocapillary barrier

Control of pulmonary circulation

the ventilation/perfusion ratio V/Q 1 Chiefly passive, no autoregulation Unique hypoxic pulmonary vasoconstriction

(HPV aka Euler-Liljestrand rfx) to regulate the DISTRIBUTION of blood flow within the lung

The function of this regulation to optimize gas exchange (oxygenation). Blood will be directed to well-ventilated lung regions from worse ventilated parts.

HPV at work…

In a radical, two compartment lung model (left lung has no ventilation in panels B and C), the advantage is obvious: with HPV (Panel C) oxygenation is less reduced in arterial blood

Hypoxic Pulmonary Vasoconstriction

J. T. Sylvester, Larissa A. Shimoda, Philip I. Aaronson, Jeremy P.

T. Ward

Physiological Reviews 2012 92:367-520

HPV is a feature of pulmonary arterial smooth musce cells

PVR: Pulmonary Vascular Resistance

PH: Pulmonary hypertension

ROCK: RhoA/Rho kinase

(Curr Opin Pharmacol 9:287-296, 2009)

We don’t know the mechanism yet.

Long-lasting hypoxia leads to pulmonary hypertension (PH)

Pulmonary hypertension can damage both the pulmonary vessels and the right ventricle.

In ICU-s, NO (~ 20 ppm) added to the ventilatory gas mixture can alleviate PH.

Metabolic and endocrine functions of the lung.

The ~100 m2 surface area microvascular bed that is connected to the systemic circulation in series, will affect the composition of the blood in addition to the blood gases.

Many of the vasoactive substances that are washed out of the organs will be degraded by the pulmonary microvascular endothelium, so they would NOT have a hormonal effect (see next slide)

This is the site of angiotensin II hormone synthesis from angiotensin I (by ACE)

Metabolic clearance by pulmonary endothelium

Serotonin > 95%

TxA2, PGE2, LTB4 >90%

Bradykinin >80 % (also by ACE!)

These effects are specific: histamine, prostacyclin for instance are not inactivated

Organs of the systemic circulation

Today: coronary circulation and muscle circulationRenal circulation: renal physiology (55)Splanchnic circulation: GIS physiology (68)Cutaneous circulation: thermoregulation (86)Fetal circulation: reproductive physiology (91)Cerebral circulation: CNS physiology (93)

Distribution of cardiac output in the systemic circulation

brain

heart

liver +splanchnic

kidney

muscle

skin

other

total

Organ weight % flow ml/min CO% O2 uptake (ml/min) %

+ 1200 +20

2

0,5

2

0,5

50

3

42

Simplified distribution of resting CO

Cerebral + coronary blood flow = 20%

Renal blood flow = 20%

Skeletal muscle blood flow = 20%

Splanchnic blood flow = 20%

Skin blood flow and the rest = 20%

Coronary circulation

Anatomical considerations

Left and right coronaries (85-15 % of blood flow, respectively)

in the left ventricle, blood vessels are compressed during systole, most blood flow in this region occurs during diastole.

This effect is not homogenous in the venticle: the SUBENDOCARDIUM is most vulnerable!

Left

CoBF

Right

CoBF

Aortic

pressure

Systole diastole

MABP

Mean flow

Mean flow

Zero flow

Zero flow

Transmural pressure!

brain

heart

liver +splanchnic

kidney

muscle

skin

other

total

Organ weight % flow ml/min CO% O2 uptake (ml/min) %

+ 1200 +20

2

0,5

2

0,5

50

3

42

5% of CO, 10% of Oxygen consumption, AVDO2 is more than double of body average: Metabolic challenge!

Regulation of coronary circulation

The resting tone of the arterioles is determined by basal tone, there is NO sympathethic vasoconstrictor TONE

Pronounced autoregulation of blood flow

Blood flow is regulated by metabolitesreleased from cardiomyocytes (includingadenosine), important role for endothelial NO

Since oxygen extraction is maximal (up to 80% instead of average 25% elsewhere), increased metabolism MUST be supported by increased flow

rest exercise

Pyruvic acid,

ketone bodies

amino acids

Free fatty acids

Free fatty acids

Substrates of cardiac energy metabolism

Adaptation of coronary circulation to exercise

The increase in CO is chiefly produced by the increased cardiac pump function stimulated by in sympathethic activity.

The increased sympathethic stimulation leads to increased metabolic activity that is eliciting vasodilation through the increased release of metabolites. The coronary blood flow increases proportionaly with the CO (~5%)

Role for a direct autonomic vascular effect is unimportant

Cardiac work

Two components:1. Pressure-volume work (PxV) – the heart

makes form the low pressure blood (stroke volume) high pressure blood – 85%

2. Kinetic work – (1/2 m x v2) -15% increases momentum of blood

W = 1.182 Nm (J) every systole Power: P ~ 1.4 W (J/s) Efficiency: 15-40 %

Circulation in skeletal muscle

brain

heart

liver +splanchnic

kidney

muscle

skin

other

total

Organ weight % flow ml/min CO% O2 uptake (ml/min) %

+ 1200 +20

2

0,5

2

0,5

50

3

42

At rest, the oxygen consumption is a tiny fraction (2%) of the heart muscle per unit weight, also the blood flow (4%)

Skeletal muscle blood flow: quantitative data

The skeletal musculature is ~ half of body weight

15-20% of resting CO, <1 l/min,

80% of CO during physical exercise: up to 20-22 l/min

Responsible for 20% resting oxygen consumption, 80% of maximal oxygen consumption, can increase by 50-75 fold during work! (catches up with heart muscle)

skin

Heart, brain

Splanchnic and renal

flow

Skeletal muscle

Oxygen consumption (l/min)

Cardiac output

Regulation of skeletal muscle circulation

Sympathetic vasoconstrictor tone: systemic MABP regulation

Sympathetic cholinergic vasodilation: anticipatory vasodilation?!

Active hyperemia: metabolic regulation (K+, acidosis, adenosine, PGE2)

Significant capillary recruitment during exercise

Active hyperemia in working skeletal muscle

To observe: initial (anticipatory) flow increase, vascular compression by contractions (transmural pressure!), the developing active hyperemia in between the contractions that diminishes after the stop of the exercise.

Central venous pressure

Mean arterial pressure

Heart rate

Stroke volume

Cardiac output

TP resistance

Splanchnic blood

flow

Venous tone (symp)

Adaptation to physical exercise

Sympathetic tone increases, and arterioles dilate in active muscles.Net effects:TPR decreasesCO increasessystolic and mean arterial pressure increases, diastolic barely changes if any. Redistribution: splanchnic (and skin) flow decreases to limit decrease in TPR

exercise

These factors also affect baroreceptor sensitivity

Guyton diagram at work: cardiac output change during exercise

Sympathetic stimulation of the heart

Sympathetic venoconstriction

Decreased total peripheral resistance