Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or

organ Organ may refer to: Biology * Organ (biology), a part of an organism Musical instruments * Organ (music), a family of keyboard musical instruments characterized by sustained tone ** Electronic organ, an electronic keyboard instrument ** Hammond ...

of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e.

hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

and microvascular dysfunction. It also implies local

in a part of a body resulting from constriction (such as vasoconstriction, thrombosis, or embolism). 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, ...

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 (ath ...

(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,

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 ar ...

paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...

, 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 dige ...

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 Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...

is a very late sign of acute arterial ischemia and signals the death of nerves 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 t ...

may occur as a result of nerve damage. Because nerves are extremely sensitive to

, limb

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 o ...

may persist after revascularization and may be permanent.

Cardiac ischemia

Cardiac ischemia may be asymptomatic or may cause chest pain, known as angina pectoris. 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 that ...

, receives insufficient blood flow. This most frequently results from atherosclerosis, which is the long-term accumulation of cholesterol-rich plaques in the coronary arteries. In most Western countries,

Ischemic heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

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 (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 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. The ...

Brain

Brain ischemia is insufficient blood flow to the brain, and can be

acute Acute may refer to: Science and technology * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf morphology * Acute (medicine), a disease that it is of short duration and of recent onset. ** Acute toxicity, the adverse eff ...

or chronic. Acute ischemic stroke 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 called vascular dementia. A sudden, brief episode (symptoms lasting only minutes) of ischemia affecting the brain is called a transient ischemic attack (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, ...

may results in

or chronic limb threatening ischemia.

Cutaneous

Reduced blood flow to the skin layers may result in mottling 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 Renovascular hypertension is a condition in which high blood pressure is caused by the kidneys' hormonal response to narrowing of the arteries supplying the kidneys. When functioning properly this hormonal axis regulates blood pressure. Due to lo ...

, acute renal failure, progressive azotemia, and acute pulmonary edema. 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, vo ...

and a need for renal surgery.

Causes

Ischemia is a vascular disease 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,

, or extremity that, if untreated, can lead to tissue death. It can be caused by embolism, thrombosis of an atherosclerotic artery, or trauma. Venous problems like venous outflow obstruction and low-flow states can cause acute arterial ischemia. An aneurysm is one of the most frequent causes of acute arterial ischemia. Other causes are heart conditions including myocardial infarction,

mitral valve disease Mitral regurgitation (MR), also known as mitral insufficiency or mitral incompetence, is a form of valvular heart disease in which the mitral valve is insufficient and does not close properly when the heart pumps out blood.

, chronic atrial fibrillation, cardiomyopathies, 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 are prone to develop.Lewis. S.L (2008). ''Medical-Surgical Nursing'' (7th ed.). Vascular disorder. pp. 907–908.

Occlusion

The thrombi may dislodge and may travel anywhere in the circulatory system, 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 breathing ...

, an acute arterial occlusion causing the oxygen and

distal to the embolus to decrease suddenly. The degree and extent of symptoms depend on the size and location of the obstruction, the occurrence of clot fragmentation with embolism to smaller vessels, and the degree of peripheral arterial disease (PAD). * Thromboembolism (blood clots) * Embolism (foreign bodies in the circulation, e.g. amniotic fluid embolism)

Trauma

Traumatic injury to an extremity may produce partial or total occlusion of a vessel from compression,

shearing Sheep shearing is the process by which the woollen fleece of a sheep is cut off. The person who removes the sheep's wool is called a '' shearer''. Typically each adult sheep is shorn once each year (a sheep may be said to have been "shorn" or ...

, or laceration. Acute arterial occlusion may develop as a result of

arterial dissection A dissection is a tear within the wall of a blood vessel, which allows blood to separate the wall layers. Usually, a dissection is an arterial wall dissection, but vein wall dissections (VWD) have been documented. By separating a portion of the ...

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 t ...

or aorta or as a result of iatrogenic arterial injury (e.g., after angiography).

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) * Atherosclerosis (lipid-laden plaques obstructing the lumen of arteries) * Hypoglycemia (lower than normal level of glucose) * Tachycardia (abnormally rapid beating of the heart) *

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. Radia ...

* Hypotension (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 Con ...

, heart failure) * Outside compression of a blood vessel, e.g. by a tumor or in the case of superior mesenteric artery syndrome * Sickle cell disease (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 measure ...

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 or improper cold compression therapy * Tourniquet application * An increased level of glutamate receptor 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 appea ...

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 diseas ...

* rupture of significant blood vessels supplying a tissue or organ. * Anemia 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, 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 sev ...

or opioids, 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 damage is the result of the build-up of

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 ( ...

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

l damage, and eventual leakage of autolyzing proteolytic

enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

into the cell and surrounding tissues. Restoration of blood supply to ischemic tissues can cause additional damage known as reperfusion injury 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 spont ...

and reactive oxygen species that damage cells. It also brings more calcium ions to the tissues causing further calcium overloading and can result in potentially fatal cardiac arrhythmias and also accelerates cellular

self-destruction Self-destructive behavior is any behavior that is harmful or potentially harmful towards the person who engages in the behavior. Self-destructive behaviors have been shown by many people throughout the years. It is on a continuum, with one extr ...

. The restored blood flow also exaggerates the inflammation response of damaged tissues, causing white blood cells 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 the ...

, thrombolysis,

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. 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 treatm ...

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 the ...

, recently formed emboli may be treated with catheter-directed thrombolysis using intra-arterial infusion of a thrombolytic agent (e.g., recombinant tissue plasminogen activator ( tPA), streptokinase, or urokinase). A percutaneous catheter inserted into the femoral artery and threaded to the site of the clot is used to infuse the drug. Unlike

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 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 from some persistent source, such as chronic atrial fibrillation, treatment includes long-term oral

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

. 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. Ischemic stroke is at times treated with various levels of statin 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 founded in 1998 to fight

ischemic heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

s through education and research.Infarct Combat Project website
accessed October 26, 2015.

Etymology and pronunciation

The word ''ischemia'' () is from Greek ἴσχαιμος ''iskhaimos'' 'staunching blood', from ἴσχω ''iskhο'' 'keep back, restrain' and αἷμα ''haima'' 'blood'.

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