Circulation and the Heart

An adult human holds about 5 litres of blood. At rest, each side of the heart pumps roughly that much every minute, and over 7,000 litres in a day. The same few litres go round again and again. This lesson asks how a pump does that, why animals build it differently, and how Harvey worked out that blood circulates at all.

Bulk flow, open and closed

You saw in size, scale and surface that diffusion is quick over micrometres and far too slow over centimetres. A large animal relies on bulk flow: a pump drives a whole fluid along, and diffusion does only the last short step. A circulatory system is that pump, the fluid and the spaces it flows through. Fluid flows from higher pressure to lower, so a pump works by making a pressure difference.

There are two broad plans. In an open circulatory system, the fluid, called hemolymph because it is blood and tissue fluid in one, leaves the vessels and flows through the hemocoel, a set of body spaces that bathe the organs directly. In a closed circulatory system, blood stays inside vessels, and exchange happens across the thin walls of capillaries, the smallest vessels.

Insects such as grasshoppers and Drosophila have open systems. A tubular heart along the back pumps hemolymph forward into the hemocoel; it drifts back over the organs and re-enters the heart through small valved openings, the ostia. Insect hemolymph carries little oxygen, because air reaches the tissues mostly through a network of air tubes, the tracheae (see gas exchange). Most molluscs, such as snails and clams, are also open.

Open and closed do not split invertebrates from vertebrates. Earthworms are closed, with muscular vessels that pump. Squid and octopuses, which are molluscs, are closed too, with two branchial hearts that push blood through the gills and a systemic heart that sends it to the body. All vertebrates are closed. (See animal body plans.)

One circuit or two: fish, frog, python, crocodile, bird, mammal

In single circulation, blood passes through the heart once per loop. In double circulation, it passes through twice: once on a pulmonary circuit to the gas-exchange organ and back, and once on a systemic circuit to the rest of the body and back.

Teleost fish (most bony fish, such as trout) have single circulation. Blood fills one atrium (a receiving chamber), which fills one ventricle (a pumping chamber). The ventricle drives blood through the gill capillaries, where it picks up oxygen, and the same push carries it on to the body. Narrow gill capillaries resist flow, so pressure falls across them, and the body is supplied at a lower pressure than the ventricle makes.

Frogs have two atria and one ventricle. The right atrium receives body blood, the left lung blood, and the ventricle feeds a pulmocutaneous circuit (lungs and skin, since frog skin exchanges gas too) and a systemic circuit. The two streams are thought to stay partly separate in the ventricle, though some mixing occurs.

Pythons have one ventricle, partly divided by a muscular ridge. Wang and colleagues (2003) recorded pressures in anesthetized Python molurus and found that the ridge separates the ventricle into regions with different pressures during contraction. You will work their numbers in the design problem.

Crocodilians have four chambers, but the right ventricle opens into both the pulmonary artery and a left aorta, and a small opening, the foramen of Panizza, joins the two aortae near their roots. When resistance in the lungs rises, blood from the right ventricle can leave by the left aorta and bypass the lungs, a shunt.

Birds and mammals have four chambers and fully separate circuits. Each group reached this independently; birds keep the right arch of the aorta, mammals the left. Reading that history needs a tree; see reading phylogenetic trees.

None of these hearts is a step toward the mammal’s. A frog heart that can send blood to the skin, or a crocodile heart that can bypass the lungs, works well in its own animal.

Through the mammalian heart, valve by valve

An artery carries blood away from the heart and a vein carries it toward the heart, whatever its oxygen content. “Right” and “left” mean the animal’s right and left. In a mammal after birth, the route is:

1. The superior and inferior venae cavae bring oxygen-poor blood from the body to the right atrium.
2. It passes the tricuspid valve into the right ventricle.
3. The right ventricle pushes it through the pulmonary valve into the pulmonary trunk and arteries, to the lungs.
4. The pulmonary veins return oxygen-rich blood to the left atrium.
5. It passes the mitral valve into the left ventricle.
6. The left ventricle pushes it through the aortic valve into the aorta, and on to the body.

So the pulmonary artery carries oxygen-poor blood and the pulmonary veins oxygen-rich blood. Each valve opens when pressure behind it exceeds pressure ahead, and closes when that reverses.

Systole is the contraction phase of a chamber and diastole its relaxation phase. For the adult human left ventricle at rest, one beat runs through four phases:

• Filling. Ventricular pressure is below atrial pressure, so the mitral valve is open and blood flows in; the atrium’s own contraction adds the last part.
• Isovolumic contraction. The ventricle contracts. Its pressure rises above atrial pressure and the mitral valve closes, but it is still below aortic pressure, so the aortic valve stays shut. With both closed, the volume cannot change.
• Ejection. Ventricular pressure passes aortic pressure (about 80 mmHg), the aortic valve opens, and blood leaves. Both peak near 120 mmHg.
• Isovolumic relaxation. The ventricle relaxes, its pressure falls below the aorta’s, and the aortic valve closes. Both valves are shut until ventricular pressure drops below atrial pressure and the mitral valve opens again.

So in “120 over 80 mmHg”, the 80 is the aorta’s lowest pressure, not the ventricle’s, which falls to a few mmHg as it fills. The right ventricle runs the same cycle against the low resistance of the lungs and peaks near 25 mmHg. It ejects the same volume at a fifth of the pressure.

Harvey’s argument by numbers

Before 1628 the standard account, from Galen, held that blood was made continually from food in the liver and used up by the tissues. In De Motu Cordis, William Harvey tested it. He tied ligatures on the human arm: a tight one stopped the pulse below it, while a looser one still let the arteries drive blood in but stopped its return, so the veins below swelled. Blood enters a limb by arteries and leaves by veins. Pressing along a vein showed that its valves pass blood only toward the heart. Then he calculated: even with small guesses per beat, the heart passes more blood in half an hour than the veins hold at once, more than food could replace.

That ruled in circulation and ruled out continual manufacture, but did not show how arteries connect to veins: Marcello Malpighi saw capillaries in the frog lung in 1661.

Worked problem. Redo Harvey’s calculation with illustrative numbers for an adult human at rest. Assume a steady state, a heart rate of 75 beats per min, an end-diastolic volume (EDV, the ventricle’s volume when full) of 120 mL and an end-systolic volume (ESV, the volume left after ejection) of 50 mL.

stroke volume = EDV - ESV and cardiac output = heart rate x stroke volume and ejection fraction = stroke volume / EDV

1. Stroke volume. 120 mL - 50 mL = 70 mL per beat.
2. Cardiac output. 75 beats per min x 70 mL per beat = 5,250 mL per min, or 5.25 L per min. This is the output of one ventricle. The left and right ventricles pump in series, so over time their outputs are equal and are not added.
3. Ejection fraction. 70 / 120 = 0.583, or 58.3 percent.
4. Harvey’s comparison. Assume 5.0 L of blood in the body. The whole volume passes through one side of the heart in 5.0 / 5.25 = 0.95 min, about 57 seconds. In half an hour that side pumps 5.25 x 30 = 157.5 L, more than 30 times the body’s blood. In a day, 5.25 x 1,440 = 7,560 L.

Harvey’s conclusion survives even if you halve every number.

Step Step 0 of 14: press Step to start at the venae cavae

Heart rate 75 beats per min End-diastolic volume (EDV) 120 mL End-systolic volume (ESV) 50 mL held at least 10 mL below EDV

Stroke volume = EDV - ESV

Cardiac output = heart rate x stroke volume

Ejection fraction = stroke volume / EDV

Time for 5.0 L of blood to pass one side of the heart

In half an hour (30 min)

In a day (1,440 min)

In this sketch: adult human at rest, steady state, illustrative numbers, 5.0 L of blood in the body, one ventricle's output; slider ends go beyond the lesson's worked values and are not data; boxes and arrows are a schematic, not anatomy.

The rule to keep: stroke volume = EDV - ESV, cardiac output = heart rate x stroke volume, and because the left and right ventricles pump in series their outputs are equal over time, so one ventricle's output is the figure to use and the two are never added.

Pacemaker, conduction and cardiac output

In mammals each beat starts in the sinoatrial (SA) node, a patch of specialized muscle in the wall of the right atrium near the entry of the superior vena cava. Its cells drift slowly upward in voltage until they reach the threshold for an impulse, fire, and start again. That drift, the prepotential, sets the heart rate. In rabbit SA node tissue, Brown and DiFrancesco (1980) recorded a current active over the pacemaker voltage range that adrenaline increased. How impulses are made is in the action potential.

Excitation spreads across both atria, then reaches the atrioventricular (AV) node, where conduction slows. A textbook schematic for adult humans places this AV delay inside the PR interval on an electrocardiogram, an interval that also includes the spread across the atria. The delay lets the atria finish contracting before the ventricles start. Excitation then runs down the bundle of His, its right and left branches, and the Purkinje fibres, which spread excitation through the ventricle walls.

Heart rate is changed mainly by autonomic nerves: sympathetic nerves speed it, and the vagus nerve, which is parasympathetic, slows it. The control circuits, including the baroreflex, are in the hypothalamus and autonomic system, Otto Loewi’s frog hearts in transmitter systems, and how adrenaline speeds the pacemaker inside the cell in cAMP and PKA.

Stroke volume is changed by filling and by contractility. Preload is how much the ventricle is filled and stretched before it contracts. By the Frank-Starling relation, more filling gives a larger stroke volume over the normal range. Sympathetic stimulation raises contractility, the strength of contraction at a given filling, and so shifts that relation upward. How vessels set the pressure the heart pumps against is in blood and vessels.

Design problem

Wang and colleagues (2003) reported systemic and pulmonary pressures of 75.7 and 11.6 cm H2O in Python molurus (the abstract does not say whether these are mean or systolic values). A python has one ventricle. Does one ventricle mean one pressure? Convert the values to mmHg (1 mmHg = 1.36 cm H2O), say what they imply about how the ventricle works, and design a measurement that would test your answer.

One way to do it

Convert: 75.7 / 1.36 = 55.7 mmHg, and 11.6 / 1.36 = 8.5 mmHg. The systemic value is about 6.5 times the pulmonary one (75.7 / 11.6 = 6.5, the same ratio in either unit).

One open chamber would push the same pressure into both outflows, so one pressure cannot give both values: the ventricle behaves as two regions during contraction. Wang and colleagues’ intraventricular recordings pointed to the muscular ridge, and Jensen and colleagues (2010), imaging python hearts by ultrasound and angioscopy, saw the ridge press against a structure called the bulbuslamelle during systole and divide the ventricle by function.

To test it, record pressure in both regions at once through the beat: separate systolic peaks support functional division. Compare a frog. Separate pressures do not rule out some mixing of blood, so measure that separately.