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:''This is an article about circulation in animals. For transport in plants, see [[Vascular tissue]]. For the band, see [[Circulatory System]].''
:''This is an article about circulation in animals. For transport in plants, see [[Vascular tissue]]. For the band, see [[Circulatory System]].''
[[Image:Grafik blutkreislauf.jpg|thumb|right|Human circulatory system. arteries shown as red, veins blue.]]
<!--[[Image:Grafik blutkreislauf.jpg|thumb|right|Human circulatory system. arteries shown as red, veins blue.]]-->


The '''circulatory system''' (also called the '''cardiovascular system''', in vertebrates) is an [[organ (anatomy)|organ system]] that moves [[blood]] and [[lymph]] to and from the [[cell (biology)|cells]] of the body through a network of hollow vessels.  The circulation of blood brings oxygen and food molecules to cells, and removes carbon dioxide and the waste products of [[metabolism]] from them. Blood circulation also helps stabilize the body temperature and [[pH]] (part of [[homeostasis]]).  The circulatory system provides for the widespread transportation of[[ immune cells]] and [[antibodies]] that fight germs and toxins, as well as [[hormone]]s and other signal molecules that have functions throughout the body. The circulation of [[lymph]] is particularly important for the body's absorption of fat from the [[small intestine]], and the movement of excess fluid as well as [[white cell]]s and [[proteins]]. The lymph and blood circulations are connected and the contents of both sets of vessels are ultimately moved by the pumping of the [[heart]].  
The '''circulatory system''' (also called the '''cardiovascular system''', in vertebrates) is an [[organ (anatomy)|organ system]] that moves [[blood]] and [[lymph]] ''to and from'' the [[cell (biology)|cells]] of the body through a network of hollow vessels.  The circulation of blood brings oxygen and food molecules to cells, and removes carbon dioxide and the waste products of [[metabolism]] from them. Blood circulation also helps stabilize the body temperature and [[pH]] (part of [[homeostasis]]).  The circulatory system provides for the widespread transportation of[[ immune cells]] and [[antibodies]] that fight germs and toxins, as well as the transport of [[hormone]]s and other signal molecules that have functions throughout the body. The circulation of [[lymph]] is particularly important for the body's absorption of fat from the [[small intestine]], and the movement of excess fluid as well as [[white cell]]s and [[proteins]]. The lymph and blood circulations are connected and the contents of both sets of vessels are ultimately moved by the pumping of the [[heart]].  


In this article, the human circulatory system is taken as a model.
In this article, the human circulatory system is taken as a model. Other types of circulatory systems are briefly discussed.


==Closed circulatory system: overview in vertebrates==
==Closed circulatory system: overview in vertebrates==
The main components of the circulatory system are the [[heart]], the [[blood]], and the [[blood vessel]]s, the [[lymph]] and the [[lymphatic vessel]]s. The blood and lymphatic circulations are connected, and between them, account for the entire systemic circulation. 
There are some parts of the body that have circulating fluids that are ''not'' in direct contact with the systemic circulation, but are more protected. These include the [[cerebrospinal fluid]] of the [[central nervous system]] that supplies the [[brain]] and [[spinal cord]], and the fluid of the [[anterior chamber]] of the [[eye]].
The circulatory systems of all [[vertebrate]]s, as well as of [[annelid]]s (for example, [[earthworm]]s) and [[cephalopod]]s ([[squid]] and [[octopus]]) are ''closed'', meaning that the blood never leaves the system of blood vessels consisting of [[Artery|arteries]], [[capillaries]] and [[vein]]s.  
The circulatory systems of all [[vertebrate]]s, as well as of [[annelid]]s (for example, [[earthworm]]s) and [[cephalopod]]s ([[squid]] and [[octopus]]) are ''closed'', meaning that the blood never leaves the system of blood vessels consisting of [[Artery|arteries]], [[capillaries]] and [[vein]]s.  


[[Artery|Arteries]] carry blood away from the heart , and [[vein]]s bring blood back to the heart. The heart is a hollow muscular organ that is always pumping, and is responsible for the movement of the blood. Blood passes from [[Artery|arteries]] to [[vein]]s through [[capillaries]], which are the thinnest and most numerous of the blood vessels. The capillaries are a netweok of blood vessels that are something like the low pressure tributaries that irrigate the soil, it is through the capillaries that nutrients and oxygen pass out to cells, and it is through the capillaries that carbon dioxide and wastes pass from the cells into the blood.
The main components of the circulatory system are the [[heart]], the [[blood]], and the blood vessels, the [[lymph]] and the [[lymphatic vessel]]s. The blood and lymphatic circulations are connected, and between them, account for the entire systemic circulation. This section looks at an overview of the patterns of blood and lymph flow in the vertebrate body.  
 
Now the arteries bring blood not just to tissues in general, but to each organ. Some of the organs have special functions that make the blood leaving them in veins quite different than the blood that enters them in arteries. For example the [[lungs]] inhale air that passes through to the [[alveoli]], small sacs of pulmonary tissue with a very rich capillary network. The arteries that bring blood to the lungs are called the pulmonary arteries and the veins that drain blood from the lungs are called the pulmonary veins. When blood enters that alveolar capillary network from the arterole end, it is pretty much depleted of oxygen but is full of carbon dioxide. The capillary blood gives up that carbon dioxide to the lung, and takes on oxygen. The blood that collects from the venule end of the alveolar capillary bed is oxygen rich and quite low in carbon dioxide. This bright red blood drains into the heart through the large [[pulmonary veins]] and is pumped from the heart into the systemic circulation through the largest artery of the body, the [[aorta]].


[[Artery|Arteries]] carry blood ''away from the heart'', and [[vein]]s bring blood ''back to the heart''. The heart is a hollow muscular organ that is always pumping, and is responsible for moving the blood around the body. Blood passes from [[Artery|arteries]] to [[vein]]s through [[capillaries]], which are the thinnest and most numerous of the blood vessels. The capillaries are a network of blood vessels, something like the low-pressure tributaries that irrigate the soil, it is through the capillaries that nutrients and oxygen pass out to cells, and it is through the capillaries that carbon dioxide and wastes pass from the cells into the blood.


Now the arteries bring blood not just to tissues in general, but to each organ. Some of the organs have special functions that make the blood leaving them in veins quite different than the blood that enters them in arteries. For example the [[lungs]] inhale air that passes through to the [[alveoli]], small sacs of pulmonary tissue with a very rich capillary network. These alveoli are where the actual exchange of gasses takes place in the lungs,inhaled oxygen being taken in by the body, and carbon dioxide given off with exhalation. The ''pulmonary arteries'' bring blood to the lungs and the ''pulmonary veins'' drain blood from the lungs. When blood first enters alveolar capillaries, it is pretty much depleted of oxygen but is full of carbon dioxide. The capillary blood gives up that carbon dioxide to the lung, and takes on oxygen from the air sac of the alveolus. The blood that collects from the venule end of the alveolar capillary bed is then rich in oxygen and quite low in carbon dioxide. This bright red blood drains into the heart through the large [[pulmonary veins]], and is then pumped from the heart into the systemic circulation through the largest artery of the body, the [[aorta]]. The aorta sends blood to all of the organs of the body except the lungs. (The pulmonary arteries come to the lungs directly from the heart, from the right ventricle.) 


In this way, the circulation of the blood supplies oxygen continuously to all of the cells of the body, and delivers waste gasses to the lungs for expulsion from the body. Because of their special function of gas exchange, the oxygen saturation of blood in the pulmonary arteries and veins is different from every other artery and vein. The pulmonary artery has oxygen-poor blood, and the pulmonary vein has oxygen-rich blood.


The systems of [[fish]], [[amphibian]]s, [[reptile]]s, [[bird]]s and [[mammal]]s show various stages of [[evolution]].
The kidneys 'filter' the blood by removing some waste products. The renal arteries are full of metabolic waste products, like the [[urea]] that is a breakdown product from proteins, and these are filtered out in the small functional waste removing units of the kidney (the [[glomeruli]]). The blood that leaves the venules from the capillary networks of the glomeruli is free of these wastes, and clean blood collects in the renal veins to be brought back to the heart.  


In fish, the system has only one circuit, with the blood being pumped through the capillaries of the [[gill]]s and on to the capillaries of the body tissues. This is known as ''single'' circulation. The heart of fish is therefore only a single pump (consisting of two chambers).
The digestive system breaks down and absorbs food, and so the veins that drain the capillary beds of the tissues of the stomach and of the intestines are rich in nutrients and absorbed fluids.  


In amphibians and most reptiles, a [[double circulatory system]] is used, but the heart is not always completely separated into two pumps. Amphibians have a three-chambered heart.
===The brain, spinal cord and eye===
Some parts of the body have circulating fluids that are ''not'' in direct contact with the systemic circulation. These include the [[cerebrospinal fluid]] of the [[central nervous system]] that supplies the [[brain]] and [[spinal cord]], and the fluid of the [[anterior chamber]] of the [[eye]].


Birds and mammals show complete separation of the heart into two pumps, for a total of four heart chambers; it is thought that the four-chambered heart of birds evolved independently of that of mammals.
===The heart and vessels in the different classes of vertebrates===
The systems of [[fish]], [[amphibian]]s, [[reptile]]s, [[bird]]s and [[mammal]]s have some important differences. In fish, the system has only one circuit; blood is pumped through the capillaries of the [[gill]]s and on to the capillaries of the body tissues. This is known as ''single'' circulation. The fish heart therefore has just one pump and just two chambers. Amphibians and most reptiles have a [[double circulatory system]], but the heart is not always completely separated into two pumps. Amphibians have a three-chambered heart. In birds and mammals, the heart always contains two pumps, with four heart chambers; it is thought that the four-chambered heart of birds evolved independently from that of mammals.


===Human circulatory system ===
===Human circulatory system ===
Poorly oxygenated blood collects in two major veins: the [[superior vena cava]] and the [[inferior vena cava]]. The superior and inferior vena cava empty into the [[right atrium]]. The coronary sinus which brings blood back from the heart itself also empties into the right atrium. The right atrium is the larger of the two atria although it recieves the same amount of blood. The blood is then pumped through the tricuspid atrioventricular valve into the [[right ventricle]]. From the right ventricle, blood is pumped through the pulmonary semi-lunar valve into the [[pulmonary trunk]]. This blood leaves the heart by the pulmonary arteries and travels through the lungs (where it is oxygenated) and into the [[pulmonary veins]]. The oxygenated blood then enters the [[left atrium]]. The blood then travels through the bicuspid valve, also called mitral valve, into the [[left ventricle]]. The left ventricle is thicker and more muscular than the right ventricle because it pumps blood at a higher pressure. From the left ventricle, blood is pumped through the semi-lunar valve into the [[aorta]]. Once the blood goes through systemic circulation, peripheral tissues will extract oxygen from the blood, which will again be collected inside the vena cava and the process will continue. Peripheral tissues do not fully deoxygenate the blood, thus venous blood does have oxygen, only in a lower concentration as arterial blood.
Poorly oxygenated blood collects in two major veins: the [[superior vena cava]] and the [[inferior vena cava]], which empty into the [[right atrium]]. The coronary sinus, which brings blood back from the heart, also empties into the right atrium. The right atrium is the larger of the two atria although it receives the same amount of blood. The blood is then pumped through the tricuspid atrioventricular valve into the [[right ventricle]]; and from there, through the pulmonary semi-lunar valve into the [[pulmonary trunk]]. This blood leaves the heart by the pulmonary arteries and travels through the lungs (where it is oxygenated), into the [[pulmonary veins]]. The oxygenated blood then enters the [[left atrium]] and travels through the bicuspid valve (also called the mitral valve) into the [[left ventricle]]. The left ventricle is thicker and more muscular than the right ventricle because it pumps blood at a higher pressure. From the left ventricle, blood is pumped through the semi-lunar valve into the [[aorta]]. As the blood circulates around the body, peripheral tissues extract oxygen from the blood. Peripheral tissues do not fully deoxygenate the blood, thus venous blood has some oxygen, but much less than arterial blood.
By: Hector Medina


==Measurement techniques==
==Measurement techniques==
Line 43: Line 43:


==History of discovery==
==History of discovery==
The valves of the heart were discovered by a physician of the Hippocratean school around the [[4th century BC]]. However their function was not properly understood then. Because blood pools in the veins after death, arteries look empty. Ancient anatomists assumed they were filled with air and that they were for transport of air.
The valves of the heart were discovered by a physician of the Hippocratean school in about the 4th century BCE, but their function was not properly understood then. Because blood pools in the veins after death, arteries look empty, and ancient anatomists assumed they were filled with air and that they were for transport of air.


[[Herophilus]] distinguished veins from arteries but thought that the pulse was a property of arteries themselves. Erasistratus observed that arteries that were cut during life bleed. He ascribed the fact to the phenomenon that air escaping from an artery is replaced with blood that entered by very small vessels between veins and arteries. Thus he apparently postulated capillaries but with reversed flow of blood.
[[Herophilus]] distinguished veins from arteries, but thought that the pulse was a property of the arteries themselves; he did not realise that it reflected the beating of the heart. Erasistratus observed that arteries bled when they were cut during life and postulated that this was because when air escaped from an artery, it was rapidly replaced by blood that entered by very small vessels between veins and arteries. Thus he apparently postulated capillaries but with reversed flow of blood.


The [[2nd century]] AD Greek physician, [[Galen]] knew that blood vessels carried blood and identified venous (dark red) and arterial (brighter and thinner) blood, each with distinct and separate functions. Growth and energy were derived from venous blood created in the liver from chyle, while arterial blood gave vitality by containing pneuma (air) and originated in the heart. Blood flowed from both creating organs to all parts of the body where it was consumed and there was no return of blood to the heart or liver. The heart did not pump blood around, the heart's motion sucked blood in during diastole and the blood moved by the pulsation of the arteries themselves.
By the 2nd century CE, the Greek physician [[Galen]] knew that blood vessels carried blood and identified venous (dark red) and arterial (brighter and thinner) blood, each with distinct and separate functions. Growth and energy were derived from venous blood created in the liver from what was then called chyle, while arterial blood gave vitality by containing pneuma (air) and originated in the heart. Blood flowed from both creating organs to all parts of the body where it was consumed and there was no return of blood to the heart or liver. The heart did not pump blood around, the heart's motion sucked blood in during diastole and the blood moved by the pulsation of the arteries.


Galen believed that the arterial blood was created by venous blood passing from the left ventricle to the right by passing through '[[pore]]s' in the interventricular septum, air passed from the lungs via the pulmonary artery to the left side of the heart. As the arterial blood was created 'sooty' vapors were created and passed to the lungs also via the pulmonary artery to be exhaled.
Galen thought that the arterial blood was created by venous blood passing from the left ventricle to the right by passing through '[[pore]]s' in the interventricular septum, air passed from the lungs via the pulmonary artery to the left side of the heart. As the arterial blood was created 'sooty' vapors were created and passed to the lungs also via the pulmonary artery to be exhaled.


[[Ibn Nafis]] in [[1242]] was the first person to accurately describe the process of blood circulation in the human body. Contemporary drawings of this process have survived. In [[1552]], [[Michael Servetus]] described the same, and [[Realdo Colombo]] proved the concept. All these results were not widely accepted however.
[[Ibn Nafis]] in 1242 was the first person to accurately describe the process of blood circulation in the human body. Contemporary drawings of this process have survived. In 1552, [[Michael Servetus]] described the same, and [[Realdo Colombo]] proved the concept. All these results were not widely accepted however.


Finally [[William Harvey]], a pupil of [[Hieronymus Fabricius]] (who had earlier described the valves of the veins without recognizing their function), performed a sequence of experiments and announced in [[1628]] the discovery of the human circulatory system as his own and published [[Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus|an influential book]] about it. This work with its essentially correct exposition slowly convinced the medical world. Harvey was not able to identify the capillary system connecting arteries and veins; these were later described by [[Marcello Malpighi]].
Finally [[William Harvey]], a pupil of [[Hieronymus Fabricius]] (who had earlier described the valves of the veins without recognizing their function), performed a sequence of experiments and announced in 1628 the discovery of the human circulatory system as his own and published [[Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus|an influential book]] about it. This work with its essentially correct exposition slowly convinced the medical world. Harvey was not able to identify the capillary system connecting arteries and veins; these were later described by [[Marcello Malpighi]].


==See also==
==See also==
Line 69: Line 69:


== References ==
== References ==
* Iskandar, Albert Z. [http://www.islamset.com/isc/nafis/iskandar.html "Comprehensive Book on the Art of Medicine by Ibn al-Nafis"]. Retrieved [[May 2]] [[2005]]. <!-- Used to verify date of Ibn Nafis description of circulatory system as 1242 -->
* Iskandar, Albert Z. [http://www.islamset.com/isc/nafis/iskandar.html "Comprehensive Book on the Art of Medicine by Ibn al-Nafis"]. Retrieved May 2, 2005. <!-- Used to verify date of Ibn Nafis description of circulatory system as 1242 -->[[Category:Suggestion Bot Tag]]
 
{{cardiovascular_system}}
{{organ_systems}}
 
[[Category:Cardiovascular system]]
[[Category:Exercise physiology]]
 
[[Category:CZ Live]]

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This is an article about circulation in animals. For transport in plants, see Vascular tissue. For the band, see Circulatory System.

The circulatory system (also called the cardiovascular system, in vertebrates) is an organ system that moves blood and lymph to and from the cells of the body through a network of hollow vessels. The circulation of blood brings oxygen and food molecules to cells, and removes carbon dioxide and the waste products of metabolism from them. Blood circulation also helps stabilize the body temperature and pH (part of homeostasis). The circulatory system provides for the widespread transportation ofimmune cells and antibodies that fight germs and toxins, as well as the transport of hormones and other signal molecules that have functions throughout the body. The circulation of lymph is particularly important for the body's absorption of fat from the small intestine, and the movement of excess fluid as well as white cells and proteins. The lymph and blood circulations are connected and the contents of both sets of vessels are ultimately moved by the pumping of the heart.

In this article, the human circulatory system is taken as a model. Other types of circulatory systems are briefly discussed.

Closed circulatory system: overview in vertebrates

The circulatory systems of all vertebrates, as well as of annelids (for example, earthworms) and cephalopods (squid and octopus) are closed, meaning that the blood never leaves the system of blood vessels consisting of arteries, capillaries and veins.

The main components of the circulatory system are the heart, the blood, and the blood vessels, the lymph and the lymphatic vessels. The blood and lymphatic circulations are connected, and between them, account for the entire systemic circulation. This section looks at an overview of the patterns of blood and lymph flow in the vertebrate body.

Arteries carry blood away from the heart, and veins bring blood back to the heart. The heart is a hollow muscular organ that is always pumping, and is responsible for moving the blood around the body. Blood passes from arteries to veins through capillaries, which are the thinnest and most numerous of the blood vessels. The capillaries are a network of blood vessels, something like the low-pressure tributaries that irrigate the soil, it is through the capillaries that nutrients and oxygen pass out to cells, and it is through the capillaries that carbon dioxide and wastes pass from the cells into the blood.

Now the arteries bring blood not just to tissues in general, but to each organ. Some of the organs have special functions that make the blood leaving them in veins quite different than the blood that enters them in arteries. For example the lungs inhale air that passes through to the alveoli, small sacs of pulmonary tissue with a very rich capillary network. These alveoli are where the actual exchange of gasses takes place in the lungs,inhaled oxygen being taken in by the body, and carbon dioxide given off with exhalation. The pulmonary arteries bring blood to the lungs and the pulmonary veins drain blood from the lungs. When blood first enters alveolar capillaries, it is pretty much depleted of oxygen but is full of carbon dioxide. The capillary blood gives up that carbon dioxide to the lung, and takes on oxygen from the air sac of the alveolus. The blood that collects from the venule end of the alveolar capillary bed is then rich in oxygen and quite low in carbon dioxide. This bright red blood drains into the heart through the large pulmonary veins, and is then pumped from the heart into the systemic circulation through the largest artery of the body, the aorta. The aorta sends blood to all of the organs of the body except the lungs. (The pulmonary arteries come to the lungs directly from the heart, from the right ventricle.)

In this way, the circulation of the blood supplies oxygen continuously to all of the cells of the body, and delivers waste gasses to the lungs for expulsion from the body. Because of their special function of gas exchange, the oxygen saturation of blood in the pulmonary arteries and veins is different from every other artery and vein. The pulmonary artery has oxygen-poor blood, and the pulmonary vein has oxygen-rich blood.

The kidneys 'filter' the blood by removing some waste products. The renal arteries are full of metabolic waste products, like the urea that is a breakdown product from proteins, and these are filtered out in the small functional waste removing units of the kidney (the glomeruli). The blood that leaves the venules from the capillary networks of the glomeruli is free of these wastes, and clean blood collects in the renal veins to be brought back to the heart.

The digestive system breaks down and absorbs food, and so the veins that drain the capillary beds of the tissues of the stomach and of the intestines are rich in nutrients and absorbed fluids.

The brain, spinal cord and eye

Some parts of the body have circulating fluids that are not in direct contact with the systemic circulation. These include the cerebrospinal fluid of the central nervous system that supplies the brain and spinal cord, and the fluid of the anterior chamber of the eye.

The heart and vessels in the different classes of vertebrates

The systems of fish, amphibians, reptiles, birds and mammals have some important differences. In fish, the system has only one circuit; blood is pumped through the capillaries of the gills and on to the capillaries of the body tissues. This is known as single circulation. The fish heart therefore has just one pump and just two chambers. Amphibians and most reptiles have a double circulatory system, but the heart is not always completely separated into two pumps. Amphibians have a three-chambered heart. In birds and mammals, the heart always contains two pumps, with four heart chambers; it is thought that the four-chambered heart of birds evolved independently from that of mammals.

Human circulatory system

Poorly oxygenated blood collects in two major veins: the superior vena cava and the inferior vena cava, which empty into the right atrium. The coronary sinus, which brings blood back from the heart, also empties into the right atrium. The right atrium is the larger of the two atria although it receives the same amount of blood. The blood is then pumped through the tricuspid atrioventricular valve into the right ventricle; and from there, through the pulmonary semi-lunar valve into the pulmonary trunk. This blood leaves the heart by the pulmonary arteries and travels through the lungs (where it is oxygenated), into the pulmonary veins. The oxygenated blood then enters the left atrium and travels through the bicuspid valve (also called the mitral valve) into the left ventricle. The left ventricle is thicker and more muscular than the right ventricle because it pumps blood at a higher pressure. From the left ventricle, blood is pumped through the semi-lunar valve into the aorta. As the blood circulates around the body, peripheral tissues extract oxygen from the blood. Peripheral tissues do not fully deoxygenate the blood, thus venous blood has some oxygen, but much less than arterial blood.

Measurement techniques

Health and disease

For more information, see: Cardiovascular disease.


History of discovery

The valves of the heart were discovered by a physician of the Hippocratean school in about the 4th century BCE, but their function was not properly understood then. Because blood pools in the veins after death, arteries look empty, and ancient anatomists assumed they were filled with air and that they were for transport of air.

Herophilus distinguished veins from arteries, but thought that the pulse was a property of the arteries themselves; he did not realise that it reflected the beating of the heart. Erasistratus observed that arteries bled when they were cut during life and postulated that this was because when air escaped from an artery, it was rapidly replaced by blood that entered by very small vessels between veins and arteries. Thus he apparently postulated capillaries but with reversed flow of blood.

By the 2nd century CE, the Greek physician Galen knew that blood vessels carried blood and identified venous (dark red) and arterial (brighter and thinner) blood, each with distinct and separate functions. Growth and energy were derived from venous blood created in the liver from what was then called chyle, while arterial blood gave vitality by containing pneuma (air) and originated in the heart. Blood flowed from both creating organs to all parts of the body where it was consumed and there was no return of blood to the heart or liver. The heart did not pump blood around, the heart's motion sucked blood in during diastole and the blood moved by the pulsation of the arteries.

Galen thought that the arterial blood was created by venous blood passing from the left ventricle to the right by passing through 'pores' in the interventricular septum, air passed from the lungs via the pulmonary artery to the left side of the heart. As the arterial blood was created 'sooty' vapors were created and passed to the lungs also via the pulmonary artery to be exhaled.

Ibn Nafis in 1242 was the first person to accurately describe the process of blood circulation in the human body. Contemporary drawings of this process have survived. In 1552, Michael Servetus described the same, and Realdo Colombo proved the concept. All these results were not widely accepted however.

Finally William Harvey, a pupil of Hieronymus Fabricius (who had earlier described the valves of the veins without recognizing their function), performed a sequence of experiments and announced in 1628 the discovery of the human circulatory system as his own and published an influential book about it. This work with its essentially correct exposition slowly convinced the medical world. Harvey was not able to identify the capillary system connecting arteries and veins; these were later described by Marcello Malpighi.

See also

External links

References