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Ischemia or ischaemia is a restriction in
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...
supply to any tissue,
muscle group Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
, or organ of the body, causing a shortage of
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
that is needed for
cellular metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
(to keep tissue alive). Ischemia is generally caused by problems with
blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide awa ...
s, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. It also implies local hypoxia in a part of a body resulting from
constriction Constriction is a method used by various snake species to kill or subdue their prey. Although some species of venomous and mildly venomous snakes do use constriction to subdue their prey, most snakes which use constriction lack venom. The snake i ...
(such as
vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...
,
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...
, or
embolism An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid (amni ...
). Ischemia causes not only insufficiency of oxygen, but also reduced availability of
nutrient A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
s and inadequate removal of
metabolic waste Metabolic wastes or excrements are substances left over from metabolic processes (such as cellular respiration) which cannot be used by the organism (they are surplus or toxic), and must therefore be excreted. This includes nitrogen compounds, w ...
s. Ischemia can be partial (poor
perfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deliver ...
) or total blockage. The inadequate delivery of oxygenated blood to the organs must be resolved either by treating the cause of the inadequate delivery or reducing the oxygen demand of the system that needs it. For example, patients with myocardial ischemia have a decreased blood flow to the heart and are prescribed with medications that reduce chronotrophy and ionotrophy to meet the new level of blood delivery supplied by the stenosed vasculature so that it is adequate.


Signs and symptoms

The signs and symptoms of ischemia vary, as they can occur anywhere in the body and depend on the degree to which blood flow is interrupted. For example, clinical manifestations of
acute limb ischemia Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb. Acute limb ischaemia is caused by embolism or thrombosis, or rarely by dissection or trauma. Thrombosis is usually caused by peripheral vascular disease (a ...
(which can be summarized as the "six P's") include
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
,
pallor Pallor is a pale color of the skin that can be caused by illness, emotional shock or stress, stimulant use, or anemia, and is the result of a reduced amount of oxyhaemoglobin and may also be visible as pallor of the conjunctivae of the eyes o ...
,
pulseless In medicine, a pulse represents the tactile arterial palpation of the cardiac cycle (heartbeat) by trained fingertips. The pulse may be palpated in any place that allows an artery to be compressed near the surface of the body, such as at the ne ...
,
paresthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias a ...
, paralysis, and poikilothermia. Without immediate intervention, ischemia may progress quickly to tissue
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dig ...
and
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the ga ...
within a few hours. Paralysis is a very late sign of acute arterial ischemia and signals the death of
nerves A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the ...
supplying the extremity.
Foot drop Foot drop is a gait abnormality in which the dropping of the forefoot happens due to weakness, irritation or damage to the deep fibular nerve (deep peroneal), including the sciatic nerve, or paralysis of the muscles in the anterior portion of ...
may occur as a result of
nerve damage Nerve injury is an injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve ...
. Because nerves are extremely sensitive to hypoxia, limb paralysis or ischemic
neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
may persist after
revascularization In medical and surgical therapy, revascularization is the restoration of perfusion to a body part or organ that has had ischemia. It is typically accomplished by surgical means. Vascular bypass and angioplasty are the two primary means of reva ...
and may be permanent.


Cardiac ischemia

Cardiac ischemia may be asymptomatic or may cause chest pain, known as
angina pectoris Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of obstru ...
. It occurs when the heart muscle, or
myocardium Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle tha ...
, receives insufficient blood flow. This most frequently results from
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no ...
, which is the long-term accumulation of cholesterol-rich plaques in the
coronary arteries The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ of ...
. In most Western countries, Ischemic heart disease is the most common cause of death in both men and women, and a major cause of hospital admissions.


Bowel

Both large and small intestines can be affected by ischemia. The blockage of blood flow to the
large intestine The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being re ...
(colon) is called
ischemic colitis Ischemic colitis (also spelled ischaemic colitis) is a medical condition in which inflammation and injury of the large intestine result from inadequate blood supply. Although uncommon in the general population, ischemic colitis occurs with greater ...
. Ischemia of the
small bowel The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through th ...
is called
mesenteric ischemia Intestinal ischemia is a medical condition in which injury to the large or small intestine occurs due to not enough blood supply. It can come on suddenly, known as acute intestinal ischemia, or gradually, known as chronic intestinal ischemia. Th ...
.


Brain

Brain ischemia Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ischemic stroke. ...
is insufficient blood flow to the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in ...
, and can be acute or chronic. Acute
ischemic stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
is a neurological emergency typically caused by a blood clot blocking blood flow in a vessel in the brain. Chronic ischemia of the brain may result in a form of
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
called
vascular dementia Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisting ...
. A sudden, brief episode (symptoms lasting only minutes) of ischemia affecting the brain is called a
transient ischemic attack A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same symptoms associated with strokes, such as weakness or numbness on one side of ...
(TIA), often called a mini-stroke. TIAs can be a warning of future strokes, with approximately 1/3 of TIA patients having a serious stroke within one year.


Limb

Inadequate blood supply to a
limb Limb may refer to: Science and technology *Limb (anatomy), an appendage of a human or animal *Limb, a large or main branch of a tree *Limb, in astronomy, the curved edge of the apparent disk of a celestial body, e.g. lunar limb *Limb, in botany, t ...
may results in
acute limb ischemia Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb. Acute limb ischaemia is caused by embolism or thrombosis, or rarely by dissection or trauma. Thrombosis is usually caused by peripheral vascular disease (a ...
or chronic limb threatening ischemia.


Cutaneous

Reduced blood flow to the skin layers may result in
mottling Mottle is a pattern of irregular marks, spots, streaks, blotches or patches of different shades or colours. It is commonly used to describe the surface of plants or the skin of animals. In plants, mottling usually consists of yellowish spots ...
or uneven, patchy discoloration of the skin.


Kidney Ischemia

Kidney Ischemia is a loss of blood flow to the kidney cells. Several physical symptoms include shrinkage of one or both kidneys, renovascular hypertension,
acute renal failure Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cla ...
, progressive azotemia, and acute
pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due to ...
. It is a disease with high mortality rate and high morbidity. Failure to treat could cause
chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...
and a need for renal surgery.


Causes

Ischemia is a
vascular disease Vascular disease is a class of diseases of the blood vessels – the arteries and veins of the circulatory system of the body. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood vessels can cause ...
involving an interruption in the arterial
blood supply The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
to a tissue, organ, or extremity that, if untreated, can lead to tissue death. It can be caused by
embolism An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid (amni ...
,
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...
of an
atherosclerotic Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no ...
artery, or trauma.
Venous Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated ...
problems like venous outflow obstruction and low-flow states can cause acute arterial ischemia. An
aneurysm An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus ( ...
is one of the most frequent causes of acute arterial ischemia. Other causes are heart conditions including
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
, mitral valve disease, chronic atrial fibrillation,
cardiomyopathies Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. ...
, and
prosthesis In medicine, a prosthesis (plural: prostheses; from grc, πρόσθεσις, prósthesis, addition, application, attachment), or a prosthetic implant, is an artificial device that replaces a missing body part, which may be lost through trau ...
, in all of which
thrombi A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
are prone to develop.Lewis. S.L (2008). ''Medical-Surgical Nursing'' (7th ed.). Vascular disorder. pp. 907–908.


Occlusion

The
thrombi A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
may dislodge and may travel anywhere in the
circulatory system The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
, where they may lead to
pulmonary embolus Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathin ...
, an acute arterial occlusion causing the oxygen and
blood supply The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
distal to the
embolus An embolus (; plural emboli; from the Greek ἔμβολος "wedge", "plug") is an unattached mass that travels through the bloodstream and is capable of creating blockages. When an embolus occludes a blood vessel, it is called an embolism or em ...
to decrease suddenly. The degree and extent of symptoms depend on the size and location of the obstruction, the occurrence of
clot A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
fragmentation with
embolism An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid (amni ...
to smaller vessels, and the degree of
peripheral arterial disease Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular diseas ...
(PAD). *
Thromboembolism Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...
(blood clots) *
Embolism An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid (amni ...
(foreign bodies in the circulation, e.g.
amniotic fluid embolism An amniotic fluid embolism (AFE) is a very uncommon childbirth (obstetric) emergency in which amniotic fluid enters the blood stream of the mother, triggering a serious reaction, which results in cardiorespiratory (heart and lung) collapse and m ...
)


Trauma

Traumatic injury An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, or o ...
to an extremity may produce partial or total occlusion of a vessel from compression, shearing, or
laceration A wound is a rapid onset of injury that involves lacerated or punctured skin (an ''open'' wound), or a contusion (a ''closed'' wound) from blunt force trauma or compression. In pathology, a ''wound'' is an acute injury that damages the epider ...
. Acute arterial occlusion may develop as a result of arterial dissection in the
carotid artery Carotid artery may refer to: * Common carotid artery, often "carotids" or "carotid", an artery on each side of the neck which divides into the external carotid artery and internal carotid artery * External carotid artery, an artery on each side of ...
or
aorta The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes ...
or as a result of
iatrogenic Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. "Iatrogenic", ''Merriam-Webster.com'', Merriam-Webster, Inc., accessed 27 ...
arterial injury (e.g., after
angiography Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perform ...
).


Other

An inadequate flow of blood to a part of the body may be caused by any of the following: * Thoracic outlet syndrome (compression of the
brachial plexus The brachial plexus is a network () of nerves formed by the anterior rami of the lower four cervical nerves and first thoracic nerve ( C5, C6, C7, C8, and T1). This plexus extends from the spinal cord, through the cervicoaxillary canal in th ...
) *
Atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no ...
(lipid-laden plaques obstructing the lumen of
arteries An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...
) *
Hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
(lower than normal level of glucose) *
Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
(abnormally rapid beating of the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to ...
) *
Radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
*
Hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
(low blood pressure, e.g. in
septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Co ...
, heart failure) * Outside compression of a blood vessel, e.g. by a
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
or in the case of
superior mesenteric artery syndrome Superior mesenteric artery (SMA) syndrome is a gastro-vascular disorder in which the third and final portion of the duodenum is compressed between the abdominal aorta (AA) and the overlying superior mesenteric artery. This rare, potentially lif ...
*
Sickle cell disease Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...
(abnormally shaped red blood cells) * Induced
g-force The gravitational force equivalent, or, more commonly, g-force, is a measurement of the type of force per unit mass – typically acceleration – that causes a perception of weight, with a g-force of 1 g (not gram in mass measur ...
s which restrict the blood flow and force the blood to the extremities of the body, as in acrobatics and military flying * Localized extreme cold, such as by
frostbite Frostbite is a skin injury that occurs when exposed to extreme low temperatures, causing the freezing of the skin or other tissues, commonly affecting the fingers, toes, nose, ears, cheeks and chin areas. Most often, frostbite occurs in the h ...
or improper
cold compression therapy Cold compression therapy, also known as hilotherapy, combines two of the principles of rest, ice, compression, elevation to reduce pain and swelling from a sports or activity injury to soft tissues and is recommended by orthopedic surgeons follo ...
*
Tourniquet A tourniquet is a device that is used to apply pressure to a limb or extremity in order to stop the flow of blood. It may be used in emergencies, in surgery, or in post-operative rehabilitation. A simple tourniquet can be made from a stick an ...
application * An increased level of
glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...
stimulation *
Arteriovenous malformation Arteriovenous malformation is an abnormal connection between arteries and veins, bypassing the capillary system. This vascular anomaly is widely known because of its occurrence in the central nervous system (usually cerebral AVM), but can appe ...
s and
peripheral artery occlusive disease Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular dise ...
* rupture of significant blood vessels supplying a tissue or organ. *
Anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...
vasoconstricts the periphery so that red blood cells cannot work internally on vital organs such as the heart, brain, etc., thus causing lack of oxygen to the periphery. * Premature discontinuation of any oral anticoagulant. *
Unconsciousness Unconsciousness is a state in which a living individual exhibits a complete, or near-complete, inability to maintain an awareness of self and environment or to respond to any human or environmental stimulus. Unconsciousness may occur as the r ...
, such as due to the ingestion of excessive doses of central depressants like
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of se ...
or
opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
s, can result in ischemia of the extremities due to unusual body positions that prevent normal circulation


Pathophysiology

Ischemia results in tissue damage in a process known as
ischemic cascade The ischemic (ischaemic) cascade is a series of biochemical reactions that are initiated in the brain and other aerobic tissues after seconds to minutes of ischemia (inadequate blood supply). This is typically secondary to stroke, injury, or cardia ...
. The damage is the result of the build-up of
metabolic waste Metabolic wastes or excrements are substances left over from metabolic processes (such as cellular respiration) which cannot be used by the organism (they are surplus or toxic), and must therefore be excreted. This includes nitrogen compounds, w ...
products, inability to maintain
cell membranes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the ...
,
mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is u ...
l damage, and eventual leakage of autolyzing
proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...
enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...
into the cell and surrounding tissues. Restoration of blood supply to ischemic tissues can cause additional damage known as
reperfusion injury Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ('' re-'' + ''perfusion'') after a period of ischemia or lack of oxygen (anoxia or hy ...
that can be more damaging than the initial ischemia. Reintroduction of blood flow brings oxygen back to the tissues, causing a greater production of
free radicals In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spo ...
and
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () ...
that damage cells. It also brings more calcium ions to the tissues causing further calcium overloading and can result in potentially fatal
cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
s and also accelerates cellular self-destruction. The restored blood flow also exaggerates the
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
response of damaged tissues, causing
white blood cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
to destroy damaged cells that may otherwise still be viable.


Treatment

Early treatment is essential to keep the affected organ viable. The treatment options include injection of an
anticoagulant Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they ...
,
thrombolysis Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive ...
,
embolectomy Embolectomy is the emergency surgical removal of emboli which are blocking blood circulation. It usually involves removal of thrombi (blood clots), and is then referred to as thrombectomy. Embolectomy is an emergency procedure often as the last res ...
, surgical revascularization, or partial amputation. Anticoagulant therapy is initiated to prevent further enlargement of the
thrombus A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
. Continuous IV
unfractionated heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treat ...
has been the traditional agent of choice. If the condition of the ischemic limb is stabilized with
anticoagulation Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they ...
, recently formed
emboli An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid (amnioti ...
may be treated with catheter-directed
thrombolysis Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive ...
using intra-arterial
infusion Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping). An infu ...
of a thrombolytic agent (e.g., recombinant tissue plasminogen activator ( tPA),
streptokinase Streptokinase (SK) is a thrombolytic medication activating plasminogen by nonenzymatic mechanism. As a medication it is used to break down clots in some cases of myocardial infarction (heart attack), pulmonary embolism, and arterial thromboembol ...
, or
urokinase Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally i ...
). A percutaneous
catheter In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cat ...
inserted into the
femoral artery The femoral artery is a large artery in the thigh and the main arterial supply to the thigh and leg. The femoral artery gives off the deep femoral artery or profunda femoris artery and descends along the anteromedial part of the thigh in the fe ...
and threaded to the site of the
clot A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
is used to infuse the drug. Unlike
anticoagulant Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they ...
s, thrombolytic agents work directly to resolve the clot over a period of 24 to 48 hours. Direct arteriotomy may be necessary to remove the clot. Surgical
revascularization In medical and surgical therapy, revascularization is the restoration of perfusion to a body part or organ that has had ischemia. It is typically accomplished by surgical means. Vascular bypass and angioplasty are the two primary means of reva ...
may be used in the setting of trauma (e.g., laceration of the artery).
Amputation Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on indi ...
is reserved for cases where limb salvage is not possible. If the patient continues to have a risk of further
embolization Embolization refers to the passage and lodging of an embolus within the bloodstream. It may be of natural origin (pathological), in which sense it is also called embolism, for example a pulmonary embolism; or it may be artificially induced ...
from some persistent source, such as chronic atrial fibrillation, treatment includes long-term oral
anticoagulation Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they ...
to prevent further acute arterial ischemic episodes. Decrease in body temperature reduces the aerobic metabolic rate of the affected cells, reducing the immediate effects of hypoxia. Reduction of body temperature also reduces the inflammation response and reperfusion injury. For frostbite injuries, limiting thawing and warming of tissues until warmer temperatures can be sustained may reduce
reperfusion injury Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ('' re-'' + ''perfusion'') after a period of ischemia or lack of oxygen (anoxia or hy ...
. Ischemic stroke is at times treated with various levels of
statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. L ...
therapy at hospital discharge, followed by home time, in an attempt to lower the risk of adverse events.


Society and culture

The Infarct Combat Project (ICP) is an international
nonprofit organization A nonprofit organization (NPO) or non-profit organisation, also known as a non-business entity, not-for-profit organization, or nonprofit institution, is a legal entity organized and operated for a collective, public or social benefit, in co ...
founded in 1998 to fight ischemic heart diseases through education and research.Infarct Combat Project website
accessed October 26, 2015.


Etymology and pronunciation

The word ''ischemia'' () is from
Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...
ἴσχαιμος ''iskhaimos'' 'staunching blood', from ἴσχω ''iskhο'' 'keep back, restrain' and αἷμα ''haima'' 'blood'.


See also

*
Infarction Infarction is tissue death ( necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct (from the ...
* Inhibitor protein * Trauma triad of death * Ischemia-reperfusion injury of the appendicular musculoskeletal system


References


Bibliography

* Elizabeth (editor)
Oxford Reference: ''Concise Medical Dictionary''
(1990, 3rd ed.). Oxford University Press: Market House Books, 1987, 2nd ed., pp. 107, {{Authority control Angiology