From Code to Clinic

Overview of cardiovascular system

Physiological rationale for the cardiovascular system

Living cells require metabolic substrates (O2, glucose, amino acids) and means to remove metabolic waste products (CO2, lactic acid). For small, single-celled organisms, the transport of such biological substances can happen via diffusion. For larger, multi-celled organisms, diffusion would be far too slow, and a system of blood vessels thus exists to transport biological substances. Blood vessels facilitate the exchange substances between blood vessels and blood, and this is the ultimate purpose of the cardiovascular, or circulatory, system.

Anatomical overview

In Latin, the cardiovascular system is known as systema cardiovasculare. The Greek kardia and the Latin cor both mean "heart". The German and Dutch words for "heart" - Herz and hart, respectively - share the same root as the Greek and Latin words. The Latin vascularis means "pertaining to blood vessels", vas meaning "vessel" and "vasculum" originally being diminutive sense (i.e. "little vessel"). Another name for the cardiovascular system is the circulatory system, in reference to the fact that the blood flows through the circuit of vessels ("circulatory" comes from the French circulatoire, meaning "moving through a circuit", the Latin circulus meaning "circular orbit" or "ring"; the Swedish blodbana makes reference to the circulatory sense of the cardiovascular system, since directly translated it literally means "blood circuit").
The cardiovascular system is made up of the heart, the blood vessels and the blood.

Cardiac anatomy

Vascular anatomy

The vascular system comprises the blood vessels. These vessels can be divided into three types: arteries (Greek arteria means "air duct", since at dissection arteries were "empty", and thought to carry air), capillaries (Latin capillus, meaning "hair" or "properly of the head", same root as caput, meaning "head"), and veins (Latin vena meaning "blood vessel", but also "a water course" and "a vein of metal"). Arteries lead away from the heart and distribute oxygenated blood and nutrients to tissues and organs. Inside tissues and organs, capillaries form the exchange interface at which gases and substances can be exchanged. Veins lead to the heart, carrying deoxygenated blood and waste. The entire network of blood vessels inside an organ is known as a vascular bed or "angioarchitecture", and the network of capillaries in an organ is a capillary bed.

Cardiovascular arrangement on a systems level

The cardiovascular system as dual circulations

On a systems level, the cardiovascular system can be considered two circulations. The minor (pulmonary) circulation (Latin circulatio minor) starts when blood leaves the right ventricle. It passes through the pulmonary valve and pulmonary arteries to the lungs, undergoes gas exchange (i.e. is oxygenated), and passes through pulmonary veins to the left atrium. The major (systemic) circulation (Latin circulatio major) begins when oxygenated blood leaves the left ventricle via the aortic valve, and is transported throughout the body. The blood returns to the heart mainly via the vena cavae, as deoxygenated blood, into the right atrium. The pulmonary circulation does not supply the lungs with oxygenated blood, this happens via the bronchial circulation, a part of the systemic circulation. Likewise, the heart itself is supplied with oxygenated blood via the coronary circulation, which branches off the left ventricle and aorta, and is also a part of the systemic circulation.

The cardiovascular system as central and peripheral circulations

Medicine has many examples of dividing things into something "central" and "peripheral" - central versus peripheral nervous system, peripheral neuropathy, peripheral blood, peripheral artery disease - but often the implied "central" counterpart is missing. The terms "peripheral circulation" and "peripheral vascular disease" are often used in clinical medicine. Nevertheless, it is surprisingly hard to find an actual definition of what actually constitues the peripheral circulation, and by extension what would be the central circulation. A Google search gives many examples of the usage of the term "peripheral circulation", but no definitions. Alan Burton notes in 1958 (!) that "no one seems to be able to define" peripheral circulation (Burton, 1958). The 19th edition of Harrisons Principles of internal medicine yields no definition on peripheral circulation. The Wikipedia article on the peripheral vascular system provides a definition, which comes from an American Heart Association text on peripheral vascular disease. The AHA states that peripheral vascular disease is disease of vessels "outside the heart and brain". Using this definition, it can thus be said that the "central" circulation is made up of the coronary and cerebral circulations, and that the peripheral circulation is "everything else". In other words, the peripheral circulation is made up of both the systemic and pulmonary circulation, minus those of the heart and brain.

The heart as two pumps

The heart is functionally two pumps, and the pulmonary and systemic circulations sit between these pumps. The two pumps are the right and left side of the heart. The right heart is made up of the right atrium and right ventricle, which feeds blood via the pulmonary circulation to the left heart, which is the left atrium and left ventricle. The left heart distributes blood to the rest of the body via the systemic circulation.

Series and parallel circulatory topology

The left and right heart is separated by the pulmonary and systemic circulations, and the left and right heart are thus in series with each other. Because of the in series-layout, the volume of blood ejected per time from each side of the heart (i.e. the output) must closely match the output of the other side - otherwise, major shifts of blood can occur between the circulations, which can lead to congestion, a fluid buildup, known as edema. If the left heart becomes unable to perform its pumping function (left-sided heart failure), then fluid can back up and cause congestion in lungs, pulmonary edema. If the right side of the heart fails (i.e. right-sided heart failure), then fluid can build up in lower extremities (peripheral edema), but also the abdomen (abdominal edema, commonly called ascites; Greek askos means "bag", "sac") and the liver (the resultant liver dysfunction is known as congestive hepatopathy).
Most organ systems in the body receive their blood from the aorta, and blood is generally carried away by veins that return to the vena cavae. Most major organs' circulations are thus in parallel with each other. The parallel arrangement has important consequences, because it means that blood flow changes through major vascular beds don't affect flow in other organs' vascular beds. This has the consequence that organ-specific blood flow can be controlled independently, via local regulation.

Functional overview

The cardiovascular system's functions can be considered by looking at its two component systems in separation: the "cardiac system" (i.e. the heart) and the vascular system. The heart has the primary function to contract. Such contraction is known as systole (Greek systole means "contraction"), and the heart's relaxation is called diastole (Greek diastole means "dilation"). When used without qualifier, the terms systole and diastole generally refer to ventricular contraction and relaxation, but the atria have their respective systole and diastole too.

The heart's primary function is that of a pressure generator. It receives low-pressure blood from the venous systemic and pulmonary circulations, contracts around the blood, which raises its pressure, and ejects blood into arteries of the systemic and pulmonary circulations. This pressure generation is what drives organ blood flow and the delivery of blood to capillaries, also known as perfusion. Organ blood flow is determined (1) by a pressure gradient, $\Delta P$, which is itself determined by arterial pressure minus venous pressure ($P_{arterial} - P_{venous}$), and (2) by the resistance of the vascular system.
The pressures in the cardiac system vary. The right side of the heart is a low-pressure system, where the initial systemic venous blood has a pressure of nearly 0 mmHg. Blood passes throuh the right atrium to the right ventricle mainly passively, but right atrial contraction also contributes to right ventricular filling. Right ventricular contraction (systole) ejects blood into the pulmonary arteries, creating a maximal (systolic) pressure of ~30 mmHg in the pulmonary arteries. As blood passes through the pulmonary circulation there is a pressure drop to ~10 mmHg. The left side of the heart is a high-pressure system. The left atrium receives the pulmonary venous blood, which flows into the left ventricle both passively and via left atrial contraction. The left ventricle's contraction ejects blood into the systemic circulation and raises its pressure to a systolic pressure of ~120 mmHg. When the ventricles are relaxed the lowest (diastolic) pressure is about 15 mmHg in the pulmonary artery and 80 mmHg in the systemic circulation's large arteries.
When used without qualifier, the term "blood pressure" clinically implies the pressure in large systemic circulation arteries (systemic arterial pressure), and it is this pressure that is routinely measured with a sphygmomanometer cuff on the upper arm. In Latin the arm is known as brachium, and a sphygmomanometer measures pressure in a. brachialis. The normal systemic pressure is 120/80 mmHg, systolic pressure "over" diastolic pressure.

The heart's pumping activity can be defined as cardiac output (CO or Q), which is the amount of blood ejected per ventricular contraction (stroke volume, SV, "stroke" used in the sense of "movement of a tool", e.g. movement of an oar) multiplied with the number of ventricular contractions (or "beats") per minute (heart rate, HR), so that $\frac{V_{beat}}{beat} \cdot \frac{beats}{t} = \frac{V}{t}$, where $V$ is a volume and $t$ is time, generally a minute. Cardiac output is thus the volume of blood pumped by the heart in a minute, $CO = SV \cdot HR$.

Factors that alter HR or SV will thus alter CO. The determinants of HR are the natural, electrical pacemaker cells within the heart, which spontaneously generate electrical wavefronts (action potentials) that lead to contractions (this phenomenon is called autorhythmicity). The activity of pacemaker cells is determined by autonomic nerves and hormones, neurohumoral mechanisms (the Latin humor means "liquid", in reference to the fact that hormones are suspended in a liquid [humor]; the term is a legacy of the "humoral theory" in which the body was thought to be composed of four humors, of which blood was one). Ventricular contraction leads to ejection of blood; the volume of blood ejected in a single contraction is the SV. The force of ventricular contraction, and by definition SV, is regulated by intrinsic cardiac mechanisms and by neurohumoral mechanisms.

The vascular system is made up of the body's blood vessels. These vessels have the ability to constrict and dilate, both via diameter adjustment of the vessel itself (vasoconstriction, narrowing of blood vessel, and vasodilation, widening of vessel) and via precapillary sphincters situated just before capillaries, which can decrease or completely shut off blood flow into a capillary. The vascular system's vasoconstriction and vasodilation gives it the ability to regulate arterial blood pressure, change intra-organic blood flow, regulate capillary blood pressure, and distribute blood in the body. Vascular diameter adjustments happen via the activity of vascular smooth muscle in the vessel wall. This muscle activity is regulated by the autonomic nervous system (ANS), metabolic and biochemical signals, and by vasoactive substances from the interior vessel wall (endothelium). The blood vessel diameter is thus regulated both by extrinsic factors (neurohumoral mechanisms; ANS, circulating hormones such as angiotensin II) and intrinsic factors (intrinsic smooth muscle [myogenic] mechanisms, endothelial substances [e.g. nitrogen oxide, NO], local substances [e.g. histamine], metabolic by-products [e.g. hydrogen ions, lactic acid] and tissue oxygen levels).

Even in their resting state blood vessels have a certain degree of constriction. A vessel's resting constriction relative to its maximal dilation is known as vascular tone. Vessels in organs with a large vasodilatory capacity (myocardium, skeletal muscle, intestinal circulation) have a high vascular tone, and vessels with a smaller vasodilatory capacity (brain, kidneys) have a low vascular tone.

Regulation overview

As demands on the body change, so must the cardiovascular system adapt to these changes. Changes in demand include exercise and standing up.

Arterial blood pressure is tightly regulated since it is the driver for organ perfusion. This regulation happens via neurohumoral mechanisms, which is itself controlled by the baroreceptor reflex. Like all reflexes, this reflex has an afferent part (sensor), a pathway leading to the CNS (input), an integrating center (controller), a pathway from the CNS to the target organ (output), and an efferent part (effector). The system has a desired value (set point) that it strives to maintain when the system is disturbed; in this case the set point is an appropariate arterial blood pressure.
The afferents of the baroreceptor reflex are stretch-sensitive receptors, baroreceptors, located in the carotid arteries, aorta, vena cavae, and the heart's atria. When the set point is disturbed (e.g. blood pressure decreases from normal arterial pressure), the baroreceptors react (to decreased pressure) by sending signals to the central nervous system. The CNS then reacts by sensing efferent signals to blood vessels and the heart, which constricts blood vessels and increases cardiac output. These changes restore blood pressure to its set point. These reflex adjustments happen via the autonomic nervous system. The baroreceptor reflex works as a negative feedback loop, where a "dampening" output is "fed back" to the same input system that registered a disturbance. This type of control system maintains stability.

Decreased arterial pressure also stimulates the release of hormones. These hormones increase arterial blood pressure by (1) actions on the heart and blood vessels, and (2) by increasing blood volume via renal mechanisms. The rapid ANS reflex mechanism stands in contrast to the slower hormonal renal mechanism, which happens over a timespan of hours to days. Such hormonal mechanisms include the adrenal glands' release of catecholamines (mainly adrenaline), renal release of renin (a part of the renin-angiotensin-aldosterone system [RAAS], which stimulates the formation of angiotensin II and aldosterone), and the pituitary gland's posterior lobe's (neurohyposis) release of antidiuretic hormone (ADH, also called vasopressin).

The "tropisms" of the heart

There are a number of cardiac functions that can be varied by physiological, pathological or pharmacological influences. These functions all have the suffix "-tropic", the Greek tropos meaning "to change". The functions can be positively influenced (increased) or negatively influenced (decreased). There are five "tropisms":

"Tropism" Chronotropy Inotropy Lusitropy Dromotropy Bathmotropy
Prefix meaning Greek chronos-, "referring to time" Greek ino-, “force”, “strength”, “sinew” (as in fibrous tissue) Greek lysis-, "loosing", "releasing" Greek dromos- "running", "a race" Greek bathmos-, "threshold"
Function Heart rate Force of cardiac muscle contractions (i.e. contractility) Relaxation Conduction speed through AV node Excitation threshold for action potential
Positive factors Endogenous SNS (NA), circulating adrenaline SNS (NA; affects both atria and ventricles), circulating adrenaline, calcium, insulin Calcium, catecholamines SNS (NA), circulating adrenaline SNS (NA), circulating adrenaline
Pharmacological β agonists (beta stimulating, e.g. isoprenaline), anticholinergics (e.g. atropine)
β agonists (e.g. isoprenaline), digoxin, insulin β agonists (e.g. isoprenaline) β agonists (e.g. isoprenaline) β agonists (e.g. isoprenaline), digoxin
Pathological states Ventricular hypertrophy (e.g. ventricular remodelling after myocardial infarction) Ischemia, hyperkalemia, hypocalcemia, mild hypoxia
Physiological states Respiratory sinus arrhythmia Ventricular hypertrophy (e.g. athlete's heart, pregnancy)
Negative factors Endogenous PNS (ACh) PNS (ACh; affects mainly atria) PNS (ACh) PNS (ACh)
Pharmacological β antagonists (beta blocking), digoxin, adenosine β antagonists, non-dihydropyridine calcium channel blockers (e.g. verapamil)
Digoxin, non-dihydropyridine calcium channel blockers (e.g. verapamil), adenosine
Calcium channel blockers

Pathological states Cardiomyocyte death (i.e. myocardial infarction) Ventricular diastolic dysfunction (e.g. diastolic dysfunction in heart failure with preserved ejection fraction [HFpEF]) Hypoxia, ischemia Severe hypoxia, hypokalemia, hyponatremia, hypercalcemia
Physiological states Valsalva maneuver (baroreceptor reflex-mediated, phase 1 of maneuver), respiratory sinus arrhythmia

ACh: acetylcholine; NA: noradrenaline; PNS: parasympathetic nervous system; SNS: sympathetic nervous system

Special circulations

The determinants of vascular blood flow are generally pressure differences and resistance, which are the two parameters for regulating blood flow in most of the body's tissues and organs, the "general" circulation. Some organs have additional variable features of blood flow control, and these organ circulations are the special circulations (Sawdon, 2013). The special circulations are the coronary, pulmonary, cerebral, renal and hepatic circulations.