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Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of
oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems with
blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...
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 (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 wastes. Ischemia can be partial (poor perfusion) 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
chronotropic Chronotropic effects (from ''chrono-'', meaning time, and ''tropos'', "a turn") are those that change the heart rate. Chronotropic drugs may change the heart rate and cardiac cycle, rhythm by affecting the electrical conduction system of the hea ...
and inotropic effect 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 (which can be summarized as the "six Ps") include
pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
, pallor, pulseless,
paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...
, paralysis, and poikilothermia. Without immediate intervention, ischemia may progress quickly to tissue necrosis and gangrene within a few hours. Paralysis is a very late sign of acute arterial ischemia and signals the death of nerves supplying the extremity. Foot drop may occur as a result of nerve damage. Because nerves are extremely sensitive to hypoxia, limb paralysis or ischemic
neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...
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, receives insufficient blood flow. This most frequently results from
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
, which is the long-term accumulation of cholesterol-rich plaques in the
coronary arteries The coronary arteries are the arteries, arterial blood vessels of coronary circulation, which transport oxygenated blood to the Cardiac muscle, heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any ...
. 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 Digestion, digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces befor ...
(colon) is called ischemic colitis. Ischemia of the small bowel is called mesenteric ischemia.


Brain

Brain ischemia is insufficient blood flow to the
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
, and can be acute 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 Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
called
vascular dementia Vascular dementia is dementia caused by a series of strokes. Restricted blood flow due to strokes reduces oxygen and glucose delivery to the brain, causing cell injury and neurological deficits in the affected region. Subtypes of vascular dement ...
. 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 may result in acute limb ischemia 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, 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 long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...
and a need for renal surgery.


Causes

Ischemia is a vascular disease involving an interruption in the arterial blood supply to a tissue, organ, 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 A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
, mitral valve disease, chronic atrial fibrillation, cardiomyopathies, and prosthesis, 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 In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart ...
, where they may lead to pulmonary embolus, an acute arterial occlusion causing the oxygen and blood supply 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, or laceration. Acute arterial occlusion may develop as a result of arterial dissection in the carotid artery or
aorta The aorta ( ; : aortas or aortae) is the main and largest artery in the human body, originating from the Ventricle (heart), left ventricle of the heart, branching upwards immediately after, and extending down to the abdomen, where it splits at ...
or as a result of iatrogenic 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 perfo ...
).


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 Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
(lipid-laden plaques obstructing the lumen of arteries) *
Hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes 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 tria ...
(lower than normal level of glucose) * Tachycardia (abnormally rapid beating of the
heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
) *
Radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...
, therapeutic radiation used to treat cancer can cause a delayed side effect injury in adjacent tissue via progressive, proliferative endarteritis, inflamed arterial linings that disrupt the tissue's blood supply. *
Hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
(low blood pressure, e.g. in septic shock,
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
) * 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 * Sickle cell disease (abnormally shaped red blood cells) * Induced
g-force The g-force or gravitational force equivalent is a Specific force, mass-specific force (force per unit mass), expressed in Unit of measurement, units of standard gravity (symbol ''g'' or ''g''0, not to be confused with "g", the symbol for ...
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 malformations and peripheral artery occlusive disease * 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 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 may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...
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 metabolic waste products, inability to maintain cell membranes, mitochondrial damage, and eventual leakage of autolyzing proteolytic
enzymes An enzyme () is a protein that acts as a biological catalyst 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 pro ...
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 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 arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beat ...
s and also accelerates cellular
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. The restored blood flow also exaggerates the
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
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, thrombolysis, embolectomy, surgical revascularization, or partial amputation. Anticoagulant therapy is initiated to prevent further enlargement of the
thrombus A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...
. Continuous IV unfractionated heparin has been the traditional agent of choice. If the condition of the ischemic limb is stabilized with anticoagulation, 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 In medicine, a catheter ( ) is a thin tubing (material), 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. ...
inserted into the femoral artery and threaded to the site of the clot is used to infuse the drug. Unlike anticoagulants, 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 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 anticoagulation 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. 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 A nonprofit organization (NPO), also known as a nonbusiness entity, nonprofit institution, not-for-profit organization, or simply a nonprofit, is a non-governmental (private) legal entity organized and operated for a collective, public, or so ...
founded in 1998 to fight ischemic heart disease 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'.


See also

* * * *


References


Bibliography

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


External links

* {{Authority control Angiology