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Sunday, May 9, 2021

Cardiology

From Wikipedia, the free encyclopedia

Cardiology
Heart diagram blood flow en.svg
Blood flow diagram of the human heart. Blue components indicate de-oxygenated blood pathways and red components indicate oxygenated blood pathways.
SystemCardiovascular
SubdivisionsInterventional, Nuclear
Significant diseasesHeart disease, Cardiovascular disease, Atherosclerosis, Cardiomyopathy, Hypertension (High Blood Pressure)
Significant testsBlood tests, electrophysiology study, cardiac imaging, ECG, echocardiograms, stress test
SpecialistCardiologist
GlossaryGlossary of medicine
Cardiologist
Occupation
Names
  • Physician
  • Surgeon
Occupation type
Specialty
Activity sectors
Medicine, Surgery
Description
Education required
Fields of
employment
Hospitals, Clinics

Cardiology (from Greek καρδίᾱ kardiā, "heart" and -λογία -logia, "study") is a branch of medicine that deals with the disorders of the heart as well as some parts of the circulatory system. The field includes medical diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology. Physicians who specialize in this field of medicine are called cardiologists, a specialty of internal medicine. Pediatric cardiologists are pediatricians who specialize in cardiology. Physicians who specialize in cardiac surgery are called cardiothoracic surgeons or cardiac surgeons, a specialty of general surgery.

Specializations

All cardiologists study the disorders of the heart, but the study of adult and child heart disorders are through different training pathways. Therefore, an adult cardiologist (often simply called "cardiologist") is inadequately trained to take care of children, and pediatric cardiologists are not trained to take care of adult heart disease. The surgical aspects are not included in cardiology and are in the domain of cardiothoracic surgery. For example, coronary artery bypass surgery (CABG), cardiopulmonary bypass and valve replacement are surgical procedures performed by surgeons, not cardiologists. However, the insertion of stents and pacemakers is performed by cardiologists.

Adult cardiology

Cardiology is a specialty of internal medicine. To be a cardiologist in the United States, a three-year residency in internal medicine is followed by a three-year fellowship in cardiology. It is possible to specialize further in a sub-specialty. Recognized sub-specialties in the United States by the ACGME are cardiac electrophysiology, echocardiography, interventional cardiology, and nuclear cardiology. Recognized subspecialties in the United States by the American Osteopathic Association Bureau of Osteopathic Specialists (AOABOS) include clinical cardiac electrophysiology and interventional cardiology. While in India, a person needs to undergo three years of residency in General Medicine or Pediatrics after M.B.B.S and then three years of residency in Cardiology to be a D.M/Diplomate of National Board (DNB) in Cardiology.

Per Doximity, adult cardiologists make an average of $436,849 in the United States.

Cardiac electrophysiology

Cardiac electrophysiology is the science of elucidating, diagnosing, and treating the electrical activities of the heart. The term is usually used to describe studies of such phenomena by invasive (intracardiac) catheter recording of spontaneous activity as well as of cardiac responses to programmed electrical stimulation (PES). These studies are performed to assess complex arrhythmias, elucidate symptoms, evaluate abnormal electrocardiograms, assess risk of developing arrhythmias in the future, and design treatment. These procedures increasingly include therapeutic methods (typically radiofrequency ablation, or cryoablation) in addition to diagnostic and prognostic procedures. Other therapeutic modalities employed in this field include antiarrhythmic drug therapy and implantation of pacemakers and automatic implantable cardioverter-defibrillators (AICD).

The cardiac electrophysiology study (EPS) typically measures the response of the injured or cardiomyopathic myocardium to PES on specific pharmacological regimens in order to assess the likelihood that the regimen will successfully prevent potentially fatal sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) in the future. Sometimes a series of EPS drug trials must be conducted to enable the cardiologist to select the one regimen for long-term treatment that best prevents or slows the development of VT or VF following PES. Such studies may also be conducted in the presence of a newly implanted or newly replaced cardiac pacemaker or AICD.

Clinical cardiac electrophysiology

Clinical cardiac electrophysiology is a branch of the medical specialty of cardiology and is concerned with the study and treatment of rhythm disorders of the heart. Cardiologists with expertise in this area are usually referred to as electrophysiologists. Electrophysiologists are trained in the mechanism, function, and performance of the electrical activities of the heart. Electrophysiologists work closely with other cardiologists and cardiac surgeons to assist or guide therapy for heart rhythm disturbances (arrhythmias). They are trained to perform interventional and surgical procedures to treat cardiac arrhythmia.

The training required to become an electrophysiologist is long and requires 7 to 8 years after medical school (within the U.S.). Three years of internal medicine residency, three years of Clinical Cardiology fellowship, and one to two (in most instances) years of clinical cardiac electrophysiology.

Cardiogeriatrics

Cardiogeriatrics, or geriatric cardiology, is the branch of cardiology and geriatric medicine that deals with the cardiovascular disorders in elderly people.

Cardiac disorders such as coronary heart disease, including myocardial infarction, heart failure, cardiomyopathy, and arrhythmias such as atrial fibrillation, are common and are a major cause of mortality in elderly people. Vascular disorders such as atherosclerosis and peripheral arterial disease cause significant morbidity and mortality in aged people.

Echocardiography

Echocardiography uses standard two-dimensional, three-dimensional, and Doppler ultrasound to create images of the heart.

Echocardiography has become routinely used in the diagnosis, management, and follow-up of patients with any suspected or known heart diseases. It is one of the most widely used diagnostic tests in cardiology. It can provide a wealth of helpful information, including the size and shape of the heart (internal chamber size quantification), pumping capacity, and the location and extent of any tissue damage. An echocardiogram can also give physicians other estimates of heart function, such as a calculation of the cardiac output, ejection fraction, and diastolic function (how well the heart relaxes).

Echocardiography can help detect cardiomyopathies, such as hypertrophic cardiomyopathy, dilated cardiomyopathy, and many others. The use of stress echocardiography may also help determine whether any chest pain or associated symptoms are related to heart disease. The biggest advantage to echocardiography is that it is not invasive (does not involve breaking the skin or entering body cavities) and has no known risks or side effects.

Interventional cardiology

Interventional cardiology is a branch of cardiology that deals specifically with the catheter based treatment of structural heart diseases. A large number of procedures can be performed on the heart by catheterization. This most commonly involves the insertion of a sheath into the femoral artery (but, in practice, any large peripheral artery or vein) and cannulating the heart under X-ray visualization (most commonly Fluoroscopy).

The main advantages of using the interventional cardiology or radiology approach are the avoidance of the scars and pain, and long post-operative recovery. Additionally, interventional cardiology procedure of primary angioplasty is now the gold standard of care for an acute Myocardial infarction. This procedure can also be done proactively, when areas of the vascular system become occluded from Atherosclerosis. The Cardiologist will thread this sheath through the vascular system to access the heart. This sheath has a balloon and a tiny wire mesh tube wrapped around it, and if the cardiologist finds a blockage or Stenosis, they can inflate the balloon at the occlusion site in the vascular system to flatten or compress the plaque against the vascular wall. Once that is complete a Stent is placed as a type of scaffold to hold the vasculature open permanently.

Preventive cardiology and cardiac rehabilitation

In recent times, the focus is gradually shifting to Preventive cardiology due to increased Cardiovascular Disease burden at an early age. As per WHO, 37% of all premature deaths are due to cardiovascular diseases and out of this, 82% are in low and middle income countries. Clinical cardiology is the sub specialty of Cardiology which looks after preventive cardiology and cardiac rehabilitation. Preventive cardiology also deals with routine preventive checkup though non invasive tests specifically Electrocardiography, Stress Tests, Lipid Profile and General Physical examination to detect any cardiovascular diseases at an early age while cardiac rehabilitation is the upcoming branch of cardiology which helps a person regain his overall strength and live a normal life after a cardiovascular event. A subspecialty of preventive cardiology is sports cardiology.

Pediatric cardiology

Helen B. Taussig is known as the founder of pediatric cardiology. She became famous through her work with Tetralogy of Fallot, a congenital heart defect in which oxygenated and deoxygenated blood enters the circulatory system resulting from a ventricular septal defect (VSD) right beneath the aorta. This condition causes newborns to have a bluish-tint, cyanosis, and have a deficiency of oxygen to their tissues, hypoxemia. She worked with Alfred Blalock and Vivien Thomas at the Johns Hopkins Hospital where they experimented with dogs to look at how they would attempt to surgically cure these "blue babies." They eventually figured out how to do just that by the anastomosis of the systemic artery to the pulmonary artery and called this the Blalock-Taussig Shunt.

Tetralogy of Fallot, pulmonary atresia, double outlet right ventricle, transposition of the great arteries, persistent truncus arteriosus, and Ebstein's anomaly are various congenital cyanotic heart diseases, in which the blood of the newborn is not oxygenated efficiently, due to the heart defect.

Tetralogy of Fallot

Tetralogy of Fallot

Tetralogy of Fallot is the most common congenital heart disease arising in 1–3 cases per 1,000 births. The cause of this defect is a ventricular septal defect (VSD) and an overriding aorta. These two defects combined causes deoxygenated blood to bypass the lungs and going right back into the circulatory system. The modified Blalock-Taussig shunt is usually used to fix the circulation. This procedure is done by placing a graft between the subclavian artery and the ipsilateral pulmonary artery to restore the correct blood flow.

Pulmonary atresia

Pulmonary atresia happens in 7–8 per 100,000 births and is characterized by the aorta branching out of the right ventricle. This causes the deoxygenated blood to bypass the lungs and enter the circulatory system. Surgeries can fix this by redirecting the aorta and fixing the right ventricle and pulmonary artery connection.

There are two types of pulmonary atresia, classified by whether or not the baby also has a ventricular septal defect.

  • Pulmonary atresia with an intact ventricular septum: This type of pulmonary atresia is associated with complete and intact septum between the ventricles.
  • Pulmonary atresia with a ventricular septal defect: This type of pulmonary atresia happens when a ventricular septal defect allows blood to flow into and out of the right ventricle.

Double outlet right ventricle

Double outlet right ventricle (DORV) is when both great arteries, the pulmonary artery and the aorta, are connected to the right ventricle. There is usually a VSD in different particular places depending on the variations of DORV, typically 50% are subaortic and 30%. The surgeries that can be done to fix this defect can vary due to the different physiology and blood flow in the defected heart. One way it can be cured is by a VSD closure and placing conduits to restart the blood flow between the left ventricle and the aorta and between the right ventricle and the pulmonary artery. Another way is systemic-to-pulmonary artery shunt in cases associated with pulmonary stenosis. Also, a balloon atrial septostomy can be done to fix DORV with the Taussig-Bing anomaly.

Transposition of great arteries

Dextro-transposition of the Great Arteries

There are two different types of transposition of the great arteries, Dextro-transposition of the great arteries and Levo-transposition of the great arteries, depending on where the chambers and vessels connect. Dextro-transposition happens in about 1 in 4,000 newborns and is when the right ventricle pumps blood into the aorta and deoxygenated blood enters the bloodstream. The temporary procedure is to create an atrial septal defect (ASD). A permanent fix is more complicated and involves redirecting the pulmonary return to the right atrium and the systemic return to the left atrium, which is known as the Senning procedure. The Rastelli procedure can also be done by rerouting the left ventricular outflow, dividing the pulmonary trunk, and placing a conduit in between the right ventricle and pulmonary trunk. Levo-transposition happens in about 1 in 13,000 newborns and is characterized by the left ventricle pumping blood into the lungs and the right ventricle pumping the blood into the aorta. This may not produce problems at the beginning, but will eventually due to the different pressures each ventricle uses to pump blood. Switching the left ventricle to be the systemic ventricle and the right ventricle to pump blood into the pulmonary artery can repair levo-transposition.

Persistent truncus arteriosus

Persistent truncus arteriosus is when the truncus arteriosus fails to split into the aorta and pulmonary trunk. This occurs in about 1 in 11,000 live births and allows both oxygenated and deoxygenated blood into the body. The repair consists of a VSD closure and the Rastelli procedure.

Ebstein anomaly

Ebstein's anomaly is characterized by a right atrium that is significantly enlarged and a heart that is shaped like a box. This is very rare and happens in less than 1% of congenital heart disease cases. The surgical repair varies depending on the severity of the disease.

Pediatric cardiology is a sub-specialty of pediatrics. To become a pediatric cardiologist in the United States, one must complete a three-year residency in pediatrics, followed by a three-year fellowship in pediatric cardiology. Per doximity, pediatric cardiologists make an average of $303,917 in the United States.

The heart

Blood flow through the valves

As the center focus of cardiology, the heart has numerous anatomical features (e.g., atria, ventricles, heart valves) and numerous physiological features (e.g., systole, heart sounds, afterload) that have been encyclopedically documented for many centuries.

Disorders of the heart lead to heart disease and cardiovascular disease and can lead to a significant number of deaths: cardiovascular disease is the leading cause of death in the United States and caused 24.95% of total deaths in 2008.

The primary responsibility of the heart is to pump blood throughout the body. It pumps blood from the body — called the systemic circulation — through the lungs — called the pulmonary circulation — and then back out to the body. This means that the heart is connected to and affects the entirety of the body. Simplified, the heart is a circuit of the Circulation. While plenty is known about the healthy heart, the bulk of study in cardiology is in disorders of the heart and restoration, and where possible, of function.

The heart is a muscle that squeezes blood and functions like a pump. Each part of the heart is susceptible to failure or dysfunction and the heart can be divided into the mechanical and the electrical parts.

The electrical part of the heart is centered on the periodic contraction (squeezing) of the muscle cells that is caused by the cardiac pacemaker located in the sinoatrial node. The study of the electrical aspects is a sub-field of electrophysiology called cardiac electrophysiology and is epitomized with the electrocardiogram (ECG/EKG). The action potentials generated in the pacemaker propagate throughout the heart in a specific pattern. The system that carries this potential is called the electrical conduction system. Dysfunction of the electrical system manifests in many ways and may include Wolff–Parkinson–White syndrome, ventricular fibrillation, and heart block.

The mechanical part of the heart is centered on the fluidic movement of blood and the functionality of the heart as a pump. The mechanical part is ultimately the purpose of the heart and many of the disorders of the heart disrupt the ability to move blood. Failure to move sufficient blood can result in failure in other organs and may result in death if severe. Heart failure is one condition in which the mechanical properties of the heart have failed or are failing, which means insufficient blood is being circulated.

Coronary circulation

Coronary circulation is the circulation of blood in the blood vessels of the heart muscle (myocardium). The vessels that deliver oxygen-rich blood to the myocardium are known as coronary arteries. The vessels that remove the deoxygenated blood from the heart muscle are known as cardiac veins. These include the great cardiac vein, the middle cardiac vein, the small cardiac vein and the anterior cardiac veins.

As the left and right coronary arteries run on the surface of the heart, they can be called epicardial coronary arteries. These arteries, when healthy, are capable of autoregulation to maintain coronary blood flow at levels appropriate to the needs of the heart muscle. These relatively narrow vessels are commonly affected by atherosclerosis and can become blocked, causing angina or a heart attack. The coronary arteries that run deep within the myocardium are referred to as subendocardial.

The coronary arteries are classified as "end circulation", since they represent the only source of blood supply to the myocardium; there is very little redundant blood supply, which is why blockage of these vessels can be so critical.

Cardiac examination

The cardiac examination (also called the "precordial exam"), is performed as part of a physical examination, or when a patient presents with chest pain suggestive of a cardiovascular pathology. It would typically be modified depending on the indication and integrated with other examinations especially the respiratory examination.

Like all medical examinations, the cardiac examination follows the standard structure of inspection, palpation and auscultation.

Heart disorders

Cardiology is concerned with the normal functionality of the heart and the deviation from a healthy heart. Many disorders involve the heart itself but some are outside of the heart and in the vascular system. Collectively, the two together are termed the cardiovascular system and diseases of one part tend to affect the other.

Hypertension

Hypertension, also known as "high blood pressure"", is a long term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long term high blood pressure, however, is a major risk factor for coronary artery disease, stroke, heart failure, peripheral vascular disease, vision loss, and chronic kidney disease.

Lifestyle factors can increase the risk of hypertension. These include excess salt in the diet, excess body weight, smoking, and alcohol. Hypertension can also be caused by other diseases, or as a side-effect of drugs.

Blood pressure is expressed by two measurements, the systolic and diastolic pressures, which are the maximum and minimum pressures, respectively. Normal blood pressure at rest is within the range of 100–140 millimeters mercury (mmHg) systolic and 60–90 mmHg diastolic. High blood pressure is present if the resting blood pressure is persistently at or above 140/90 mmHg for most adults. Different numbers apply to children. Ambulatory blood pressure monitoring over a 24-hour period appears more accurate than office best blood pressure measurement.

Lifestyle changes and medications can lower blood pressure and decrease the risk of health complications. Lifestyle changes include weight loss, decreased salt intake, physical exercise, and a healthy diet. If lifestyle changes are not sufficient then blood pressure medications are used. Up to three medications can control blood pressure in 90% of people. The treatment of moderate to severe high arterial blood pressure (defined as >160/100 mmHg) with medications is associated with an improved life expectancy and reduced morbidity. The effect of treatment of blood pressure between 140/90 mmHg and 160/100 mmHg is less clear, with some reviews finding benefit and others finding a lack of evidence for benefit. High blood pressure affects between 16 and 37% of the population globally. In 2010 hypertension was believed to have been a factor in 18% (9.4 million) deaths.

Essential vs Secondary hypertension

Essential hypertension is the form of hypertension that by definition has no identifiable cause. It is the most common type of hypertension, affecting 95% of hypertensive patients, it tends to be familial and is likely to be the consequence of an interaction between environmental and genetic factors. Prevalence of essential hypertension increases with age, and individuals with relatively high blood pressure at younger ages are at increased risk for the subsequent development of hypertension. Hypertension can increase the risk of cerebral, cardiac, and renal events.

Secondary hypertension is a type of hypertension which is caused by an identifiable underlying secondary cause. It is much less common than essential hypertension, affecting only 5% of hypertensive patients. It has many different causes including endocrine diseases, kidney diseases, and tumors. It also can be a side effect of many medications.

Complications of hypertension

Main complications of persistent high blood pressure

Complications of hypertension are clinical outcomes that result from persistent elevation of blood pressure. Hypertension is a risk factor for all clinical manifestations of atherosclerosis since it is a risk factor for atherosclerosis itself. It is an independent predisposing factor for heart failure, coronary artery disease, stroke, renal disease, and peripheral arterial disease. It is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries.

Cardiac arrhythmia

Cardiac arrhythmia, also known as "cardiac dysrhythmia" or "irregular heartbeat", is a group of conditions in which the heartbeat is irregular, too fast, or too slow. A heart rate that is too fast – above 100 beats per minute in adults – is called tachycardia and a heart rate that is too slow – below 60 beats per minute – is called bradycardia. Many types of arrhythmia have no symptoms. When symptoms are present these may include palpitations or feeling a pause between heartbeats. More seriously there may be lightheadedness, passing out, shortness of breath, or chest pain. While most types of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in cardiac arrest.

There are four main types of arrhythmia: extra beats, supraventricular tachycardias, ventricular arrhythmias, and bradyarrhythmias. Extra beats include premature atrial contractions, premature ventricular contractions, and premature junctional contractions. Supraventricular tachycardias include atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. Ventricular arrhythmias include ventricular fibrillation and ventricular tachycardia. Arrhythmias are due to problems with the electrical conduction system of the heart. Arrhythmias may occur in children; however, the normal range for the heart rate is different and depends on age. A number of tests can help with diagnosis including an electrocardiogram (ECG) and Holter monitor.

Most arrhythmias can be effectively treated. Treatments may include medications, medical procedures such as a pacemaker, and surgery. Medications for a fast heart rate may include beta blockers or agents that attempt to restore a normal heart rhythm such as procainamide. This later group may have more significant side effects especially if taken for a long period of time. Pacemakers are often used for slow heart rates. Those with an irregular heartbeat are often treated with blood thinners to reduce the risk of complications. Those who have severe symptoms from an arrhythmia may receive urgent treatment with a jolt of electricity in the form of cardioversion or defibrillation.

Arrhythmia affects millions of people. In Europe and North America, as of 2014, atrial fibrillation affects about 2% to 3% of the population. Atrial fibrillation and atrial flutter resulted in 112,000 deaths in 2013, up from 29,000 in 1990. Sudden cardiac death is the cause of about half of deaths due to cardiovascular disease or about 15% of all deaths globally. About 80% of sudden cardiac death is the result of ventricular arrhythmias. Arrhythmias may occur at any age but are more common among older people.

Coronary artery disease

Coronary artery disease, also known as "ischemic heart disease", is a group of diseases that includes: stable angina, unstable angina, myocardial infarction, and is one of the causes of sudden cardiac death. It is within the group of cardiovascular diseases of which it is the most common type. A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Occasionally it may feel like heartburn. Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and get better with rest. Shortness of breath may also occur and sometimes no symptoms are present. The first sign is occasionally a heart attack. Other complications include heart failure or an irregular heartbeat.

Risk factors include: high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, and excessive alcohol, among others. Other risks include depression. The underlying mechanism involves atherosclerosis of the arteries of the heart. A number of tests may help with diagnoses including: electrocardiogram, cardiac stress testing, coronary computed tomographic angiography, and coronary angiogram, among others.

Prevention is by eating a healthy diet, regular exercise, maintaining a healthy weight and not smoking. Sometimes medication for diabetes, high cholesterol, or high blood pressure are also used. There is limited evidence for screening people who are at low risk and do not have symptoms. Treatment involves the same measures as prevention. Additional medications such as antiplatelets including aspirin, beta blockers, or nitroglycerin may be recommended. Procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) may be used in severe disease. In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improve life expectancy or decreases heart attack risk.

In 2013 CAD was the most common cause of death globally, resulting in 8.14 million deaths (16.8%) up from 5.74 million deaths (12%) in 1990. The risk of death from CAD for a given age has decreased between 1980 and 2010 especially in developed countries. The number of cases of CAD for a given age has also decreased between 1990 and 2010. In the United States in 2010 about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45. Rates are higher among men than women of a given age.

Cardiac arrest

Cardiac arrest is a sudden stop in effective blood flow due to the failure of the heart to contract effectively. Symptoms include loss of consciousness and abnormal or absent breathing. Some people may have chest pain, shortness of breath, or nausea before this occurs. If not treated within minutes, death usually occurs.

The most common cause of cardiac arrest is coronary artery disease. Less common causes include major blood loss, lack of oxygen, very low potassium, heart failure, and intense physical exercise. A number of inherited disorders may also increase the risk including long QT syndrome. The initial heart rhythm is most often ventricular fibrillation. The diagnosis is confirmed by finding no pulse. While a cardiac arrest may be caused by heart attack or heart failure these are not the same.

Prevention includes not smoking, physical activity, and maintaining a healthy weight. Treatment for cardiac arrest is immediate cardiopulmonary resuscitation (CPR) and, if a shockable rhythm is present, defibrillation. Among those who survive targeted temperature management may improve outcomes. An implantable cardiac defibrillator may be placed to reduce the chance of death from recurrence.

In the United States, cardiac arrest outside of hospital occurs in about 13 per 10,000 people per year (326,000 cases). In hospital cardiac arrest occurs in an additional 209,000 Cardiac arrest becomes more common with age. It affects males more often than females. The percentage of people who survive with treatment is about 8%. Many who survive have significant disability. Many U.S. television shows, however, have portrayed unrealistically high survival rates of 67%.

Congenital heart defects

A congenital heart defect, also known as a "congenital heart anomaly" or "congenital heart disease", is a problem in the structure of the heart that is present at birth. Signs and symptoms depend on the specific type of problem. Symptoms can vary from none to life-threatening. When present they may include rapid breathing, bluish skin, poor weight gain, and feeling tired. It does not cause chest pain. Most congenital heart problems do not occur with other diseases. Complications that can result from heart defects include heart failure.

The cause of a congenital heart defect is often unknown. Certain cases may be due to infections during pregnancy such as rubella, use of certain medications or drugs such as alcohol or tobacco, parents being closely related, or poor nutritional status or obesity in the mother. Having a parent with a congenital heart defect is also a risk factor. A number of genetic conditions are associated with heart defects including Down syndrome, Turner syndrome, and Marfan syndrome. Congenital heart defects are divided into two main groups: cyanotic heart defects and non-cyanotic heart defects, depending on whether the child has the potential to turn bluish in color. The problems may involve the interior walls of the heart, the heart valves, or the large blood vessels that lead to and from the heart.

Congenital heart defects are partly preventable through rubella vaccination, the adding of iodine to salt, and the adding of folic acid to certain food products. Some defects do not need treatment. Other may be effectively treated with catheter based procedures or heart surgery. Occasionally a number of operations may be needed. Occasionally heart transplantation is required. With appropriate treatment outcomes, even with complex problems, are generally good.

Heart defects are the most common birth defect. In 2013 they were present in 34.3 million people globally. They affect between 4 and 75 per 1,000 live births depending upon how they are diagnosed. About 6 to 19 per 1,000 cause a moderate to severe degree of problems. Congenital heart defects are the leading cause of birth defect-related deaths. In 2013 they resulted in 323,000 deaths down from 366,000 deaths in 1990.

Diagnostic tests in cardiology

Diagnostic tests in cardiology are the methods of identifying heart conditions associated with healthy vs. unhealthy, pathologic heart function. The starting point is obtaining a medical history, followed by Auscultation. Then blood tests, electrophysiological procedures, and cardiac imaging can be ordered for further analysis. Electrophysiological procedures include electrocardiogram, cardiac monitoring, cardiac stress testing, and the electrophysiology study.

Saturday, May 8, 2021

Nervous system

From Wikipedia, the free encyclopedia
 
Nervous system
TE-Nervous system diagram.svg
The human nervous system
Details
Identifiers
Latinsystema nervosum
MeSHD009420
TA98A14.0.00.000
FMA7157

In biology, the nervous system is a highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes that impact the body, then works in tandem with the endocrine system to respond to such events. Nervous tissue first arose in wormlike organisms about 550 to 600 million years ago. In vertebrates it consists of two main parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and spinal cord. The PNS consists mainly of nerves, which are enclosed bundles of the long fibers or axons, that connect the CNS to every other part of the body. Nerves that transmit signals from the brain are called motor or efferent nerves, while those nerves that transmit information from the body to the CNS are called sensory or afferent. Spinal nerves serve both functions and are called mixed nerves. The PNS is divided into three separate subsystems, the somatic, autonomic, and enteric nervous systems. Somatic nerves mediate voluntary movement. The autonomic nervous system is further subdivided into the sympathetic and the parasympathetic nervous systems. The sympathetic nervous system is activated in cases of emergencies to mobilize energy, while the parasympathetic nervous system is activated when organisms are in a relaxed state. The enteric nervous system functions to control the gastrointestinal system. Both autonomic and enteric nervous systems function involuntarily. Nerves that exit from the cranium are called cranial nerves while those exiting from the spinal cord are called spinal nerves.

At the cellular level, the nervous system is defined by the presence of a special type of cell, called the neuron, also known as a "nerve cell". Neurons have special structures that allow them to send signals rapidly and precisely to other cells. They send these signals in the form of electrochemical waves traveling along thin fibers called axons, which cause chemicals called neurotransmitters to be released at junctions called synapses. A cell that receives a synaptic signal from a neuron may be excited, inhibited, or otherwise modulated. The connections between neurons can form neural pathways, neural circuits, and larger networks that generate an organism's perception of the world and determine its behavior. Along with neurons, the nervous system contains other specialized cells called glial cells (or simply glia), which provide structural and metabolic support.

Nervous systems are found in most multicellular animals, but vary greatly in complexity. The only multicellular animals that have no nervous system at all are sponges, placozoans, and mesozoans, which have very simple body plans. The nervous systems of the radially symmetric organisms ctenophores (comb jellies) and cnidarians (which include anemones, hydras, corals and jellyfish) consist of a diffuse nerve net. All other animal species, with the exception of a few types of worm, have a nervous system containing a brain, a central cord (or two cords running in parallel), and nerves radiating from the brain and central cord. The size of the nervous system ranges from a few hundred cells in the simplest worms, to around 300 billion cells in African elephants.

The central nervous system functions to send signals from one cell to others, or from one part of the body to others and to receive feedback. Malfunction of the nervous system can occur as a result of genetic defects, physical damage due to trauma or toxicity, infection, or simply senesence. The medical specialty of neurology studies disorders of the nervous system and looks for interventions that can prevent or treat them. In the peripheral nervous system, the most common problem is the failure of nerve conduction, which can be due to different causes including diabetic neuropathy and demyelinating disorders such as multiple sclerosis and amyotrophic lateral sclerosis. Neuroscience is the field of science that focuses on the study of the nervous system.

Diagram showing the major divisions of the vertebrate nervous system.

Structure

The nervous system derives its name from nerves, which are cylindrical bundles of fibers (the axons of neurons), that emanate from the brain and spinal cord, and branch repeatedly to innervate every part of the body. Nerves are large enough to have been recognized by the ancient Egyptians, Greeks, and Romans, but their internal structure was not understood until it became possible to examine them using a microscope. The author Michael Nikoletseas wrote:

"It is difficult to believe that until approximately year 1900 it was not known that neurons are the basic units of the brain (Santiago Ramón y Cajal). Equally surprising is the fact that the concept of chemical transmission in the brain was not known until around 1930 (Henry Hallett Dale and Otto Loewi). We began to understand the basic electrical phenomenon that neurons use in order to communicate among themselves, the action potential, in the 1950s (Alan Lloyd Hodgkin, Andrew Huxley and John Eccles). It was in the 1960s that we became aware of how basic neuronal networks code stimuli and thus basic concepts are possible (David H. Hubel and Torsten Wiesel). The molecular revolution swept across US universities in the 1980s. It was in the 1990s that molecular mechanisms of behavioral phenomena became widely known (Eric Richard Kandel)."

A microscopic examination shows that nerves consist primarily of axons, along with different membranes that wrap around them and segregate them into fascicles. The neurons that give rise to nerves do not lie entirely within the nerves themselves—their cell bodies reside within the brain, spinal cord, or peripheral ganglia.

All animals more advanced than sponges have nervous systems. However, even sponges, unicellular animals, and non-animals such as slime molds have cell-to-cell signalling mechanisms that are precursors to those of neurons. In radially symmetric animals such as the jellyfish and hydra, the nervous system consists of a nerve net, a diffuse network of isolated cells. In bilaterian animals, which make up the great majority of existing species, the nervous system has a common structure that originated early in the Ediacaran period, over 550 million years ago.

Cells

The nervous system contains two main categories or types of cells: neurons and glial cells.

Neurons

Structure of a typical neuron
Neuron

The nervous system is defined by the presence of a special type of cell—the neuron (sometimes called "neurone" or "nerve cell"). Neurons can be distinguished from other cells in a number of ways, but their most fundamental property is that they communicate with other cells via synapses, which are membrane-to-membrane junctions containing molecular machinery that allows rapid transmission of signals, either electrical or chemical. Many types of neuron possess an axon, a protoplasmic protrusion that can extend to distant parts of the body and make thousands of synaptic contacts; axons typically extend throughout the body in bundles called nerves.

Even in the nervous system of a single species such as humans, hundreds of different types of neurons exist, with a wide variety of morphologies and functions. These include sensory neurons that transmute physical stimuli such as light and sound into neural signals, and motor neurons that transmute neural signals into activation of muscles or glands; however in many species the great majority of neurons participate in the formation of centralized structures (the brain and ganglia) and they receive all of their input from other neurons and send their output to other neurons.

Glial cells

Glial cells (named from the Greek for "glue") are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system. In the human brain, it is estimated that the total number of glia roughly equals the number of neurons, although the proportions vary in different brain areas. Among the most important functions of glial cells are to support neurons and hold them in place; to supply nutrients to neurons; to insulate neurons electrically; to destroy pathogens and remove dead neurons; and to provide guidance cues directing the axons of neurons to their targets. A very important type of glial cell (oligodendrocytes in the central nervous system, and Schwann cells in the peripheral nervous system) generates layers of a fatty substance called myelin that wraps around axons and provides electrical insulation which allows them to transmit action potentials much more rapidly and efficiently. Recent findings indicate that glial cells, such as microglia and astrocytes, serve as important resident immune cells within the central nervous system.

Anatomy in vertebrates

Horizontal section of the head of an adult female, showing skin, skull, and brain with grey matter (brown in this image) and underlying white matter

The nervous system of vertebrates (including humans) is divided into the central nervous system (CNS) and the peripheral nervous system (PNS).

The (CNS) is the major division, and consists of the brain and the spinal cord. The spinal canal contains the spinal cord, while the cranial cavity contains the brain. The CNS is enclosed and protected by the meninges, a three-layered system of membranes, including a tough, leathery outer layer called the dura mater. The brain is also protected by the skull, and the spinal cord by the vertebrae.

The peripheral nervous system (PNS) is a collective term for the nervous system structures that do not lie within the CNS. The large majority of the axon bundles called nerves are considered to belong to the PNS, even when the cell bodies of the neurons to which they belong reside within the brain or spinal cord. The PNS is divided into somatic and visceral parts. The somatic part consists of the nerves that innervate the skin, joints, and muscles. The cell bodies of somatic sensory neurons lie in dorsal root ganglia of the spinal cord. The visceral part, also known as the autonomic nervous system, contains neurons that innervate the internal organs, blood vessels, and glands. The autonomic nervous system itself consists of two parts: the sympathetic nervous system and the parasympathetic nervous system. Some authors also include sensory neurons whose cell bodies lie in the periphery (for senses such as hearing) as part of the PNS; others, however, omit them.

The vertebrate nervous system can also be divided into areas called gray matter and white matter. Gray matter (which is only gray in preserved tissue, and is better described as pink or light brown in living tissue) contains a high proportion of cell bodies of neurons. White matter is composed mainly of myelinated axons, and takes its color from the myelin. White matter includes all of the nerves, and much of the interior of the brain and spinal cord. Gray matter is found in clusters of neurons in the brain and spinal cord, and in cortical layers that line their surfaces. There is an anatomical convention that a cluster of neurons in the brain or spinal cord is called a nucleus, whereas a cluster of neurons in the periphery is called a ganglion. There are, however, a few exceptions to this rule, notably including the part of the forebrain called the basal ganglia.

Comparative anatomy and evolution

Neural precursors in sponges

Sponges have no cells connected to each other by synaptic junctions, that is, no neurons, and therefore no nervous system. They do, however, have homologs of many genes that play key roles in synaptic function. Recent studies have shown that sponge cells express a group of proteins that cluster together to form a structure resembling a postsynaptic density (the signal-receiving part of a synapse). However, the function of this structure is currently unclear. Although sponge cells do not show synaptic transmission, they do communicate with each other via calcium waves and other impulses, which mediate some simple actions such as whole-body contraction.

Radiata

Jellyfish, comb jellies, and related animals have diffuse nerve nets rather than a central nervous system. In most jellyfish the nerve net is spread more or less evenly across the body; in comb jellies it is concentrated near the mouth. The nerve nets consist of sensory neurons, which pick up chemical, tactile, and visual signals; motor neurons, which can activate contractions of the body wall; and intermediate neurons, which detect patterns of activity in the sensory neurons and, in response, send signals to groups of motor neurons. In some cases groups of intermediate neurons are clustered into discrete ganglia.

The development of the nervous system in radiata is relatively unstructured. Unlike bilaterians, radiata only have two primordial cell layers, endoderm and ectoderm. Neurons are generated from a special set of ectodermal precursor cells, which also serve as precursors for every other ectodermal cell type.

Bilateria

A rod-shaped body contains a digestive system running from the mouth at one end to the anus at the other. Alongside the digestive system is a nerve cord with a brain at the end, near to the mouth.
Nervous system of a bilaterian animal, in the form of a nerve cord with segmental enlargements, and a "brain" at the front

The vast majority of existing animals are bilaterians, meaning animals with left and right sides that are approximate mirror images of each other. All bilateria are thought to have descended from a common wormlike ancestor that appeared in the Ediacaran period, 550–600 million years ago. The fundamental bilaterian body form is a tube with a hollow gut cavity running from mouth to anus, and a nerve cord with an enlargement (a "ganglion") for each body segment, with an especially large ganglion at the front, called the "brain".

Area of the human body surface innervated by each spinal nerve

Even mammals, including humans, show the segmented bilaterian body plan at the level of the nervous system. The spinal cord contains a series of segmental ganglia, each giving rise to motor and sensory nerves that innervate a portion of the body surface and underlying musculature. On the limbs, the layout of the innervation pattern is complex, but on the trunk it gives rise to a series of narrow bands. The top three segments belong to the brain, giving rise to the forebrain, midbrain, and hindbrain.

Bilaterians can be divided, based on events that occur very early in embryonic development, into two groups (superphyla) called protostomes and deuterostomes. Deuterostomes include vertebrates as well as echinoderms, hemichordates (mainly acorn worms), and Xenoturbellidans. Protostomes, the more diverse group, include arthropods, molluscs, and numerous types of worms. There is a basic difference between the two groups in the placement of the nervous system within the body: protostomes possess a nerve cord on the ventral (usually bottom) side of the body, whereas in deuterostomes the nerve cord is on the dorsal (usually top) side. In fact, numerous aspects of the body are inverted between the two groups, including the expression patterns of several genes that show dorsal-to-ventral gradients. Most anatomists now consider that the bodies of protostomes and deuterostomes are "flipped over" with respect to each other, a hypothesis that was first proposed by Geoffroy Saint-Hilaire for insects in comparison to vertebrates. Thus insects, for example, have nerve cords that run along the ventral midline of the body, while all vertebrates have spinal cords that run along the dorsal midline.

Worms

Earthworm nervous system. Top: side view of the front of the worm. Bottom: nervous system in isolation, viewed from above

Worms are the simplest bilaterian animals, and reveal the basic structure of the bilaterian nervous system in the most straightforward way. As an example, earthworms have dual nerve cords running along the length of the body and merging at the tail and the mouth. These nerve cords are connected by transverse nerves like the rungs of a ladder. These transverse nerves help coordinate the two sides of the animal. Two ganglia at the head (the "nerve ring") end function similar to a simple brain. Photoreceptors on the animal's eyespots provide sensory information on light and dark.

The nervous system of one very small roundworm, the nematode Caenorhabditis elegans, has been completely mapped out in a connectome including its synapses. Every neuron and its cellular lineage has been recorded and most, if not all, of the neural connections are known. In this species, the nervous system is sexually dimorphic; the nervous systems of the two sexes, males and female hermaphrodites, have different numbers of neurons and groups of neurons that perform sex-specific functions. In C. elegans, males have exactly 383 neurons, while hermaphrodites have exactly 302 neurons.

Arthropods

Internal anatomy of a spider, showing the nervous system in blue

Arthropods, such as insects and crustaceans, have a nervous system made up of a series of ganglia, connected by a ventral nerve cord made up of two parallel connectives running along the length of the belly. Typically, each body segment has one ganglion on each side, though some ganglia are fused to form the brain and other large ganglia. The head segment contains the brain, also known as the supraesophageal ganglion. In the insect nervous system, the brain is anatomically divided into the protocerebrum, deutocerebrum, and tritocerebrum. Immediately behind the brain is the subesophageal ganglion, which is composed of three pairs of fused ganglia. It controls the mouthparts, the salivary glands and certain muscles. Many arthropods have well-developed sensory organs, including compound eyes for vision and antennae for olfaction and pheromone sensation. The sensory information from these organs is processed by the brain.

In insects, many neurons have cell bodies that are positioned at the edge of the brain and are electrically passive—the cell bodies serve only to provide metabolic support and do not participate in signalling. A protoplasmic fiber runs from the cell body and branches profusely, with some parts transmitting signals and other parts receiving signals. Thus, most parts of the insect brain have passive cell bodies arranged around the periphery, while the neural signal processing takes place in a tangle of protoplasmic fibers called neuropil, in the interior.

"Identified" neurons

A neuron is called identified if it has properties that distinguish it from every other neuron in the same animal—properties such as location, neurotransmitter, gene expression pattern, and connectivity—and if every individual organism belonging to the same species has one and only one neuron with the same set of properties. In vertebrate nervous systems very few neurons are "identified" in this sense—in humans, there are believed to be none—but in simpler nervous systems, some or all neurons may be thus unique. In the roundworm C. elegans, whose nervous system is the most thoroughly described of any animal's, every neuron in the body is uniquely identifiable, with the same location and the same connections in every individual worm. One notable consequence of this fact is that the form of the C. elegans nervous system is completely specified by the genome, with no experience-dependent plasticity.

The brains of many molluscs and insects also contain substantial numbers of identified neurons. In vertebrates, the best known identified neurons are the gigantic Mauthner cells of fish. Every fish has two Mauthner cells, in the bottom part of the brainstem, one on the left side and one on the right. Each Mauthner cell has an axon that crosses over, innervating neurons at the same brain level and then travelling down through the spinal cord, making numerous connections as it goes. The synapses generated by a Mauthner cell are so powerful that a single action potential gives rise to a major behavioral response: within milliseconds the fish curves its body into a C-shape, then straightens, thereby propelling itself rapidly forward. Functionally this is a fast escape response, triggered most easily by a strong sound wave or pressure wave impinging on the lateral line organ of the fish. Mauthner cells are not the only identified neurons in fish—there are about 20 more types, including pairs of "Mauthner cell analogs" in each spinal segmental nucleus. Although a Mauthner cell is capable of bringing about an escape response individually, in the context of ordinary behavior other types of cells usually contribute to shaping the amplitude and direction of the response.

Mauthner cells have been described as command neurons. A command neuron is a special type of identified neuron, defined as a neuron that is capable of driving a specific behavior individually. Such neurons appear most commonly in the fast escape systems of various species—the squid giant axon and squid giant synapse, used for pioneering experiments in neurophysiology because of their enormous size, both participate in the fast escape circuit of the squid. The concept of a command neuron has, however, become controversial, because of studies showing that some neurons that initially appeared to fit the description were really only capable of evoking a response in a limited set of circumstances.

Function

At the most basic level, the function of the nervous system is to send signals from one cell to others, or from one part of the body to others. There are multiple ways that a cell can send signals to other cells. One is by releasing chemicals called hormones into the internal circulation, so that they can diffuse to distant sites. In contrast to this "broadcast" mode of signaling, the nervous system provides "point-to-point" signals—neurons project their axons to specific target areas and make synaptic connections with specific target cells. Thus, neural signaling is capable of a much higher level of specificity than hormonal signaling. It is also much faster: the fastest nerve signals travel at speeds that exceed 100 meters per second.

At a more integrative level, the primary function of the nervous system is to control the body. It does this by extracting information from the environment using sensory receptors, sending signals that encode this information into the central nervous system, processing the information to determine an appropriate response, and sending output signals to muscles or glands to activate the response. The evolution of a complex nervous system has made it possible for various animal species to have advanced perception abilities such as vision, complex social interactions, rapid coordination of organ systems, and integrated processing of concurrent signals. In humans, the sophistication of the nervous system makes it possible to have language, abstract representation of concepts, transmission of culture, and many other features of human society that would not exist without the human brain.

Neurons and synapses

Major elements in synaptic transmission. An electrochemical wave called an action potential travels along the axon of a neuron. When the wave reaches a synapse, it provokes release of a small amount of neurotransmitter molecules, which bind to chemical receptor molecules in the membrane of the target cell.

Most neurons send signals via their axons, although some types are capable of dendrite-to-dendrite communication. (In fact, the types of neurons called amacrine cells have no axons, and communicate only via their dendrites.) Neural signals propagate along an axon in the form of electrochemical waves called action potentials, which produce cell-to-cell signals at points where axon terminals make synaptic contact with other cells.

Synapses may be electrical or chemical. Electrical synapses make direct electrical connections between neurons, but chemical synapses are much more common, and much more diverse in function. At a chemical synapse, the cell that sends signals is called presynaptic, and the cell that receives signals is called postsynaptic. Both the presynaptic and postsynaptic areas are full of molecular machinery that carries out the signalling process. The presynaptic area contains large numbers of tiny spherical vessels called synaptic vesicles, packed with neurotransmitter chemicals. When the presynaptic terminal is electrically stimulated, an array of molecules embedded in the membrane are activated, and cause the contents of the vesicles to be released into the narrow space between the presynaptic and postsynaptic membranes, called the synaptic cleft. The neurotransmitter then binds to receptors embedded in the postsynaptic membrane, causing them to enter an activated state. Depending on the type of receptor, the resulting effect on the postsynaptic cell may be excitatory, inhibitory, or modulatory in more complex ways. For example, release of the neurotransmitter acetylcholine at a synaptic contact between a motor neuron and a muscle cell induces rapid contraction of the muscle cell. The entire synaptic transmission process takes only a fraction of a millisecond, although the effects on the postsynaptic cell may last much longer (even indefinitely, in cases where the synaptic signal leads to the formation of a memory trace).

Structure of a typical chemical synapse

There are literally hundreds of different types of synapses. In fact, there are over a hundred known neurotransmitters, and many of them have multiple types of receptors. Many synapses use more than one neurotransmitter—a common arrangement is for a synapse to use one fast-acting small-molecule neurotransmitter such as glutamate or GABA, along with one or more peptide neurotransmitters that play slower-acting modulatory roles. Molecular neuroscientists generally divide receptors into two broad groups: chemically gated ion channels and second messenger systems. When a chemically gated ion channel is activated, it forms a passage that allows specific types of ions to flow across the membrane. Depending on the type of ion, the effect on the target cell may be excitatory or inhibitory. When a second messenger system is activated, it starts a cascade of molecular interactions inside the target cell, which may ultimately produce a wide variety of complex effects, such as increasing or decreasing the sensitivity of the cell to stimuli, or even altering gene transcription.

According to a rule called Dale's principle, which has only a few known exceptions, a neuron releases the same neurotransmitters at all of its synapses. This does not mean, though, that a neuron exerts the same effect on all of its targets, because the effect of a synapse depends not on the neurotransmitter, but on the receptors that it activates. Because different targets can (and frequently do) use different types of receptors, it is possible for a neuron to have excitatory effects on one set of target cells, inhibitory effects on others, and complex modulatory effects on others still. Nevertheless, it happens that the two most widely used neurotransmitters, glutamate and GABA, each have largely consistent effects. Glutamate has several widely occurring types of receptors, but all of them are excitatory or modulatory. Similarly, GABA has several widely occurring receptor types, but all of them are inhibitory. Because of this consistency, glutamatergic cells are frequently referred to as "excitatory neurons", and GABAergic cells as "inhibitory neurons". Strictly speaking, this is an abuse of terminology—it is the receptors that are excitatory and inhibitory, not the neurons—but it is commonly seen even in scholarly publications.

One very important subset of synapses are capable of forming memory traces by means of long-lasting activity-dependent changes in synaptic strength. The best-known form of neural memory is a process called long-term potentiation (abbreviated LTP), which operates at synapses that use the neurotransmitter glutamate acting on a special type of receptor known as the NMDA receptor. The NMDA receptor has an "associative" property: if the two cells involved in the synapse are both activated at approximately the same time, a channel opens that permits calcium to flow into the target cell. The calcium entry initiates a second messenger cascade that ultimately leads to an increase in the number of glutamate receptors in the target cell, thereby increasing the effective strength of the synapse. This change in strength can last for weeks or longer. Since the discovery of LTP in 1973, many other types of synaptic memory traces have been found, involving increases or decreases in synaptic strength that are induced by varying conditions, and last for variable periods of time. The reward system, that reinforces desired behaviour for example, depends on a variant form of LTP that is conditioned on an extra input coming from a reward-signalling pathway that uses dopamine as neurotransmitter. All these forms of synaptic modifiability, taken collectively, give rise to neural plasticity, that is, to a capability for the nervous system to adapt itself to variations in the environment.

Neural circuits and systems

The basic neuronal function of sending signals to other cells includes a capability for neurons to exchange signals with each other. Networks formed by interconnected groups of neurons are capable of a wide variety of functions, including feature detection, pattern generation and timing, and there are seen to be countless types of information processing possible. Warren McCulloch and Walter Pitts showed in 1943 that even artificial neural networks formed from a greatly simplified mathematical abstraction of a neuron are capable of universal computation.

Illustration of pain pathway, from René Descartes's Treatise of Man

Historically, for many years the predominant view of the function of the nervous system was as a stimulus-response associator. In this conception, neural processing begins with stimuli that activate sensory neurons, producing signals that propagate through chains of connections in the spinal cord and brain, giving rise eventually to activation of motor neurons and thereby to muscle contraction, i.e., to overt responses. Descartes believed that all of the behaviors of animals, and most of the behaviors of humans, could be explained in terms of stimulus-response circuits, although he also believed that higher cognitive functions such as language were not capable of being explained mechanistically. Charles Sherrington, in his influential 1906 book The Integrative Action of the Nervous System, developed the concept of stimulus-response mechanisms in much more detail, and Behaviorism, the school of thought that dominated Psychology through the middle of the 20th century, attempted to explain every aspect of human behavior in stimulus-response terms.

However, experimental studies of electrophysiology, beginning in the early 20th century and reaching high productivity by the 1940s, showed that the nervous system contains many mechanisms for maintaining cell excitability and generating patterns of activity intrinsically, without requiring an external stimulus. Neurons were found to be capable of producing regular sequences of action potentials, or sequences of bursts, even in complete isolation. When intrinsically active neurons are connected to each other in complex circuits, the possibilities for generating intricate temporal patterns become far more extensive. A modern conception views the function of the nervous system partly in terms of stimulus-response chains, and partly in terms of intrinsically generated activity patterns—both types of activity interact with each other to generate the full repertoire of behavior.

Reflexes and other stimulus-response circuits

Simplified schema of basic nervous system function: signals are picked up by sensory receptors and sent to the spinal cord and brain, where processing occurs that results in signals sent back to the spinal cord and then out to motor neurons

The simplest type of neural circuit is a reflex arc, which begins with a sensory input and ends with a motor output, passing through a sequence of neurons connected in series. This can be shown in the "withdrawal reflex" causing a hand to jerk back after a hot stove is touched. The circuit begins with sensory receptors in the skin that are activated by harmful levels of heat: a special type of molecular structure embedded in the membrane causes heat to change the electrical field across the membrane. If the change in electrical potential is large enough to pass the given threshold, it evokes an action potential, which is transmitted along the axon of the receptor cell, into the spinal cord. There the axon makes excitatory synaptic contacts with other cells, some of which project (send axonal output) to the same region of the spinal cord, others projecting into the brain. One target is a set of spinal interneurons that project to motor neurons controlling the arm muscles. The interneurons excite the motor neurons, and if the excitation is strong enough, some of the motor neurons generate action potentials, which travel down their axons to the point where they make excitatory synaptic contacts with muscle cells. The excitatory signals induce contraction of the muscle cells, which causes the joint angles in the arm to change, pulling the arm away.

In reality, this straightforward schema is subject to numerous complications. Although for the simplest reflexes there are short neural paths from sensory neuron to motor neuron, there are also other nearby neurons that participate in the circuit and modulate the response. Furthermore, there are projections from the brain to the spinal cord that are capable of enhancing or inhibiting the reflex.

Although the simplest reflexes may be mediated by circuits lying entirely within the spinal cord, more complex responses rely on signal processing in the brain. For example, when an object in the periphery of the visual field moves, and a person looks toward it many stages of signal processing are initiated. The initial sensory response, in the retina of the eye, and the final motor response, in the oculomotor nuclei of the brain stem, are not all that different from those in a simple reflex, but the intermediate stages are completely different. Instead of a one or two step chain of processing, the visual signals pass through perhaps a dozen stages of integration, involving the thalamus, cerebral cortex, basal ganglia, superior colliculus, cerebellum, and several brainstem nuclei. These areas perform signal-processing functions that include feature detection, perceptual analysis, memory recall, decision-making, and motor planning.

Feature detection is the ability to extract biologically relevant information from combinations of sensory signals. In the visual system, for example, sensory receptors in the retina of the eye are only individually capable of detecting "points of light" in the outside world. Second-level visual neurons receive input from groups of primary receptors, higher-level neurons receive input from groups of second-level neurons, and so on, forming a hierarchy of processing stages. At each stage, important information is extracted from the signal ensemble and unimportant information is discarded. By the end of the process, input signals representing "points of light" have been transformed into a neural representation of objects in the surrounding world and their properties. The most sophisticated sensory processing occurs inside the brain, but complex feature extraction also takes place in the spinal cord and in peripheral sensory organs such as the retina.

Intrinsic pattern generation

Although stimulus-response mechanisms are the easiest to understand, the nervous system is also capable of controlling the body in ways that do not require an external stimulus, by means of internally generated rhythms of activity. Because of the variety of voltage-sensitive ion channels that can be embedded in the membrane of a neuron, many types of neurons are capable, even in isolation, of generating rhythmic sequences of action potentials, or rhythmic alternations between high-rate bursting and quiescence. When neurons that are intrinsically rhythmic are connected to each other by excitatory or inhibitory synapses, the resulting networks are capable of a wide variety of dynamical behaviors, including attractor dynamics, periodicity, and even chaos. A network of neurons that uses its internal structure to generate temporally structured output, without requiring a corresponding temporally structured stimulus, is called a central pattern generator.

Internal pattern generation operates on a wide range of time scales, from milliseconds to hours or longer. One of the most important types of temporal pattern is circadian rhythmicity—that is, rhythmicity with a period of approximately 24 hours. All animals that have been studied show circadian fluctuations in neural activity, which control circadian alternations in behavior such as the sleep-wake cycle. Experimental studies dating from the 1990s have shown that circadian rhythms are generated by a "genetic clock" consisting of a special set of genes whose expression level rises and falls over the course of the day. Animals as diverse as insects and vertebrates share a similar genetic clock system. The circadian clock is influenced by light but continues to operate even when light levels are held constant and no other external time-of-day cues are available. The clock genes are expressed in many parts of the nervous system as well as many peripheral organs, but in mammals, all of these "tissue clocks" are kept in synchrony by signals that emanate from a master timekeeper in a tiny part of the brain called the suprachiasmatic nucleus.

Mirror neurons

A mirror neuron is a neuron that fires both when an animal acts and when the animal observes the same action performed by another. Thus, the neuron "mirrors" the behavior of the other, as though the observer were itself acting. Such neurons have been directly observed in primate species. Birds have been shown to have imitative resonance behaviors and neurological evidence suggests the presence of some form of mirroring system. In humans, brain activity consistent with that of mirror neurons has been found in the premotor cortex, the supplementary motor area, the primary somatosensory cortex and the inferior parietal cortex. The function of the mirror system is a subject of much speculation. Many researchers in cognitive neuroscience and cognitive psychology consider that this system provides the physiological mechanism for the perception/action coupling. They argue that mirror neurons may be important for understanding the actions of other people, and for learning new skills by imitation. Some researchers also speculate that mirror systems may simulate observed actions, and thus contribute to theory of mind skills, while others relate mirror neurons to language abilities. However, to date, no widely accepted neural or computational models have been put forward to describe how mirror neuron activity supports cognitive functions such as imitation. There are neuroscientists who caution that the claims being made for the role of mirror neurons are not supported by adequate research.

Development

In vertebrates, landmarks of embryonic neural development include the birth and differentiation of neurons from stem cell precursors, the migration of immature neurons from their birthplaces in the embryo to their final positions, outgrowth of axons from neurons and guidance of the motile growth cone through the embryo towards postsynaptic partners, the generation of synapses between these axons and their postsynaptic partners, and finally the lifelong changes in synapses which are thought to underlie learning and memory.

All bilaterian animals at an early stage of development form a gastrula, which is polarized, with one end called the animal pole and the other the vegetal pole. The gastrula has the shape of a disk with three layers of cells, an inner layer called the endoderm, which gives rise to the lining of most internal organs, a middle layer called the mesoderm, which gives rise to the bones and muscles, and an outer layer called the ectoderm, which gives rise to the skin and nervous system.

Four stages in the development of the neural tube
in the human embryo

In vertebrates, the first sign of the nervous system is the appearance of a thin strip of cells along the center of the back, called the neural plate. The inner portion of the neural plate (along the midline) is destined to become the central nervous system (CNS), the outer portion the peripheral nervous system (PNS). As development proceeds, a fold called the neural groove appears along the midline. This fold deepens, and then closes up at the top. At this point the future CNS appears as a cylindrical structure called the neural tube, whereas the future PNS appears as two strips of tissue called the neural crest, running lengthwise above the neural tube. The sequence of stages from neural plate to neural tube and neural crest is known as neurulation.

In the early 20th century, a set of famous experiments by Hans Spemann and Hilde Mangold showed that the formation of nervous tissue is "induced" by signals from a group of mesodermal cells called the organizer region. For decades, though, the nature of neural induction defeated every attempt to figure it out, until finally it was resolved by genetic approaches in the 1990s. Induction of neural tissue requires inhibition of the gene for a so-called bone morphogenetic protein, or BMP. Specifically the protein BMP4 appears to be involved. Two proteins called Noggin and Chordin, both secreted by the mesoderm, are capable of inhibiting BMP4 and thereby inducing ectoderm to turn into neural tissue. It appears that a similar molecular mechanism is involved for widely disparate types of animals, including arthropods as well as vertebrates. In some animals, however, another type of molecule called Fibroblast Growth Factor or FGF may also play an important role in induction.

Induction of neural tissues causes formation of neural precursor cells, called neuroblasts. In drosophila, neuroblasts divide asymmetrically, so that one product is a "ganglion mother cell" (GMC), and the other is a neuroblast. A GMC divides once, to give rise to either a pair of neurons or a pair of glial cells. In all, a neuroblast is capable of generating an indefinite number of neurons or glia.

As shown in a 2008 study, one factor common to all bilateral organisms (including humans) is a family of secreted signaling molecules called neurotrophins which regulate the growth and survival of neurons. Zhu et al. identified DNT1, the first neurotrophin found in flies. DNT1 shares structural similarity with all known neurotrophins and is a key factor in the fate of neurons in Drosophila. Because neurotrophins have now been identified in both vertebrate and invertebrates, this evidence suggests that neurotrophins were present in an ancestor common to bilateral organisms and may represent a common mechanism for nervous system formation.

Pathology

Layers protecting the brain and spinal cord.

The central nervous system is protected by major physical and chemical barriers. Physically, the brain and spinal cord are surrounded by tough meningeal membranes, and enclosed in the bones of the skull and vertebral column, which combine to form a strong physical shield. Chemically, the brain and spinal cord are isolated by the blood–brain barrier, which prevents most types of chemicals from moving from the bloodstream into the interior of the CNS. These protections make the CNS less susceptible in many ways than the PNS; the flip side, however, is that damage to the CNS tends to have more serious consequences.

Although nerves tend to lie deep under the skin except in a few places such as the ulnar nerve near the elbow joint, they are still relatively exposed to physical damage, which can cause pain, loss of sensation, or loss of muscle control. Damage to nerves can also be caused by swelling or bruises at places where a nerve passes through a tight bony channel, as happens in carpal tunnel syndrome. If a nerve is completely transected, it will often regenerate, but for long nerves this process may take months to complete. In addition to physical damage, peripheral neuropathy may be caused by many other medical problems, including genetic conditions, metabolic conditions such as diabetes, inflammatory conditions such as Guillain–Barré syndrome, vitamin deficiency, infectious diseases such as leprosy or shingles, or poisoning by toxins such as heavy metals. Many cases have no cause that can be identified, and are referred to as idiopathic. It is also possible for nerves to lose function temporarily, resulting in numbness as stiffness—common causes include mechanical pressure, a drop in temperature, or chemical interactions with local anesthetic drugs such as lidocaine.

Physical damage to the spinal cord may result in loss of sensation or movement. If an injury to the spine produces nothing worse than swelling, the symptoms may be transient, but if nerve fibers in the spine are actually destroyed, the loss of function is usually permanent. Experimental studies have shown that spinal nerve fibers attempt to regrow in the same way as nerve fibers, but in the spinal cord, tissue destruction usually produces scar tissue that cannot be penetrated by the regrowing nerves.

Operator (computer programming)

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