Ischemia

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Ischemia
Other namesischaemia, ischæmia
Ischemia.JPG
Vascular ischemia of the toes with characteristic cyanosis
Pronunciation
Specialty Vascular surgery

Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). [3] [4] Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. [5] [6] It also implies local hypoxia in a part of a body resulting from constriction (such as vasoconstriction, thrombosis, or embolism).

Contents

Ischemia causes not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes. [7] 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 and ionotropic 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. [4] For example, clinical manifestations of acute limb ischemia (which can be summarized as the "six P's") include pain, pallor, pulseless, paresthesia, paralysis, and poikilothermia. [8]

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 may persist after revascularization and may be permanent. [9]

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. [10] 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 is the most common cause of death in both men and women, and a major cause of hospital admissions. [11] [12]

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. [13] Ischemia of the small bowel is called mesenteric ischemia. [14]

Brain

Brain ischemia is insufficient blood flow to the brain, 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. [15] Chronic ischemia of the brain may result in a form of dementia called vascular dementia. [16] 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. [17] TIAs can be a warning of future strokes, with approximately 1/3 of TIA patients having a serious stroke within one year. [17] [18]

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, [19] renovascular hypertension, [20] acute renal failure, [19] progressive azotemia, [19] and acute pulmonary edema. [19] It is a disease with high mortality rate and high morbidity. [21] Failure to treat could cause chronic kidney disease [22] and a need for renal surgery. [23]

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, mitral valve disease, chronic atrial fibrillation, cardiomyopathies, and prosthesis, in all of which thrombi are prone to develop. [9]

Occlusion

The thrombi may dislodge and may travel anywhere in the circulatory system, 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). [9]

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 or as a result of iatrogenic arterial injury (e.g., after angiography). [9]

Other

An inadequate flow of blood to a part of the body may be caused by any of the following:

Pathophysiology

Native records of contractile activity of the left ventricle of isolated rat heart perfused under Langendorff technique. Curve A - contractile function of the heart is greatly depressed after ischemia-reperfusion. Curve B - a set of short ischemic episodes (ischemic preconditioning) before prolonged ischemia provides functional recovery of contractile activity of the heart at reperfusion. Ischemic preconditioning of the heart.png
Native records of contractile activity of the left ventricle of isolated rat heart perfused under Langendorff technique. Curve A - contractile function of the heart is greatly depressed after ischemia-reperfusion. Curve B - a set of short ischemic episodes (ischemic preconditioning) before prolonged ischemia provides functional recovery of contractile activity of the heart at reperfusion.

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 into the cell and surrounding tissues. [26]

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 arrhythmias and also accelerates cellular self-destruction. 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. [27]

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. Continuous IV unfractionated heparin has been the traditional agent of choice. [9]

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 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. [9]

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. [9]

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. [28] [29]

Society and culture

The Infarct Combat Project (ICP) is an international nonprofit organization founded in 1998 to fight ischemic heart diseases through education and research. [30]

Etymology and pronunciation

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

See also

Related Research Articles

<span class="mw-page-title-main">Thrombosis</span> Formation of blood clots inside the blood vessels

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus.

<span class="mw-page-title-main">Thrombus</span> Blood clot

A thrombus, 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 cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to stop and prevent further bleeding, but can be harmful in thrombosis, when a clot obstructs blood flow through a healthy blood vessel in the circulatory system.

<span class="mw-page-title-main">Cerebrovascular disease</span> Condition that affects the arteries that supply the brain

Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.

<span class="mw-page-title-main">Infarction</span> Tissue death due to inadequate blood supply

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 Latin infarctus, "stuffed into").

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. This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the activation of chemicals produced during and after ischemia. The ischemic cascade usually goes on for two to three hours but can last for days, even after normal blood flow returns.

<span class="mw-page-title-main">Cerebral infarction</span> Stroke resulting from lack of blood flow

Cerebral infarction, also known as an ischemic stroke, is the pathologic process that results in an area of necrotic tissue in the brain. In mid to high income countries, a stroke is the main reason for disability among people and the 2nd cause of death. It is caused by disrupted blood supply (ischemia) and restricted oxygen supply (hypoxia). This is most commonly due to a thrombotic occlusion, or an embolic occlusion of major vessels which leads to a cerebral infarct. In response to ischemia, the brain degenerates by the process of liquefactive necrosis.

An embolus, is described as a free-floating mass, located inside blood vessels that can travel from one site in the blood stream to another. An embolus can be made up of solid, liquid, or gas. Once these masses get "stuck" in a different blood vessel, it is then known as an "embolism." An embolism can cause ischemia—damage to an organ from lack of oxygen. A paradoxical embolism is a specific type of embolism in which the embolus travels from the right side of the heart to the left side of the heart and lodges itself in a blood vessel known as an artery. Thus, it is termed "paradoxical" because the embolus lands in an artery, rather than a vein.

<span class="mw-page-title-main">Watershed stroke</span> Medical condition

A watershed stroke is defined as a brain ischemia that is localized to the vulnerable border zones between the tissues supplied by the anterior, posterior and middle cerebral arteries. The actual blood stream blockage/restriction site can be located far away from the infarcts. Watershed locations are those border-zone regions in the brain supplied by the major cerebral arteries where blood supply is decreased. Watershed strokes are a concern because they comprise approximately 10% of all ischemic stroke cases. The watershed zones themselves are particularly susceptible to infarction from global ischemia as the distal nature of the vasculature predisposes these areas to be most sensitive to profound hypoperfusion.

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. It is a sub-type of stroke along with subarachnoid hemorrhage and intracerebral hemorrhage.

Animal models of ischemic stroke are procedures inducing cerebral ischemia. The aim is the study of basic processes or potential therapeutic interventions in this disease, and the extension of the pathophysiological knowledge on and/or the improvement of medical treatment of human ischemic stroke. Ischemic stroke has a complex pathophysiology involving the interplay of many different cells and tissues such as neurons, glia, endothelium, and the immune system. These events cannot be mimicked satisfactorily in vitro yet. Thus a large portion of stroke research is conducted on animals.

Ischemic preconditioning (IPC) is an experimental technique for producing resistance to the loss of blood supply, and thus oxygen, to tissues of many types. In the heart, IPC is an intrinsic process whereby repeated short episodes of ischaemia protect the myocardium against a subsequent ischaemic insult. It was first identified in 1986 by Murry et al. This group exposed anesthetised open-chest dogs to four periods of 5 minute coronary artery occlusions followed by a 5-minute period of reperfusion before the onset of a 40-minute sustained occlusion of the coronary artery. The control animals had no such period of “ischaemic preconditioning” and had much larger infarct sizes compared with the dogs that did. The exact molecular pathways behind this phenomenon have yet to be fully understood.

<span class="mw-page-title-main">Hemorrhagic infarct</span> Medical condition

A hemorrhagic infarct is determined when hemorrhage is present around an area of infarction. Simply stated, an infarction is an area of dead tissue or necrosis. When blood escapes outside of the vessel (extravasation) and re-perfuses back into the tissue surrounding the infarction, the infarction is then termed a hemorrhagic infarct (infarction). Hemorrhagic infarcts can occur in any region of the body, such as the head, trunk and abdomen-pelvic regions, typically arising from their arterial blood supply being interrupted by a blockage or compression of an artery.

<span class="mw-page-title-main">Intestinal ischemia</span> Restriction of blood flow to the small intestine resulting in injury

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 acute form of the disease often presents with sudden severe abdominal pain and is associated with a high risk of death. The chronic form typically presents more gradually with abdominal pain after eating, unintentional weight loss, vomiting, and fear of eating.

No reflow phenomenon is the failure of blood to reperfuse an ischemic area after the physical obstruction has been removed or bypassed. The underlying mechanism is related to arterial microvasculature damage. It is primarily seen during percutaneous coronary intervention (PCI) in the setting of acute myocardial infarction (AMI), but has also been observed in other organs, including the brain and kidneys. Coronary no-reflow phenomenon is specifically related to reduced antegrade coronary blood flow despite proximal coronary artery patency. It is an independent predictor of worse clinical outcomes including heart failure, fatal arrhythmias, myocardial infarction, and increased mortality rates.

Embolectomy is the emergency interventional or surgical removal of emboli which are blocking blood circulation. It usually involves removal of thrombi, and is then referred to as thromboembolectomy or thrombectomy. Embolectomy is an emergency procedure often as the last resort because permanent occlusion of a significant blood flow to an organ leads to necrosis. Other involved therapeutic options are anticoagulation and thrombolysis.

<span class="mw-page-title-main">Acute limb ischaemia</span> Occurs when there is a sudden lack of blood flow to a limb

Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb, within 14 days of symptoms onset. It is different from another condition which is more chronic called critical limb ischemia (CLD). CLD is the end stage of peripheral vascular disease where there is still some collateral circulation (alternate circulation pathways} that bring some blood to the distal parts of the limbs. While limbs in both acute and chronic limb ischemia may be pulseless, a chronically ischemic limb is typically warm and pink due to a well-developed collateral artery network and does not need emergency intervention to avoid limb loss.

<span class="mw-page-title-main">Arterial embolism</span> Interruption of blood flow to an organ

Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood, the major type of embolus being a blood clot (thromboembolism). Sometimes, pulmonary embolism is classified as arterial embolism as well, in the sense that the clot follows the pulmonary artery carrying deoxygenated blood away from the heart. However, pulmonary embolism is generally classified as a form of venous embolism, because the embolus forms in veins. Arterial embolism is the major cause of infarction.

Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis.

Kidney ischemia is a disease with a high morbidity and mortality rate. Blood vessels shrink and undergo apoptosis which results in poor blood flow in the kidneys. More complications happen when failure of the kidney functions result in toxicity in various parts of the body which may cause septic shock, hypovolemia, and a need for surgery. What causes kidney ischemia is not entirely known, but several pathophysiology relating to this disease have been elucidated. Possible causes of kidney ischemia include the activation of IL-17C and hypoxia due to surgery or transplant. Several signs and symptoms include injury to the microvascular endothelium, apoptosis of kidney cells due to overstress in the endoplasmic reticulum, dysfunctions of the mitochondria, autophagy, inflammation of the kidneys, and maladaptive repair.

<span class="mw-page-title-main">Arterial occlusion</span>

Arterial occlusion is a condition involving partial or complete blockage of blood flow through an artery. Arteries are blood vessels that carry oxygenated blood to body tissues. An occlusion of arteries disrupts oxygen and blood supply to tissues, leading to ischemia. Depending on the extent of ischemia, symptoms of arterial occlusion range from simple soreness and pain that can be relieved with rest, to a lack of sensation or paralysis that could require amputation.

References

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  2. ↑ Entry "ischemia" in Merriam-Webster Online Dictionary .
  3. ↑ Merck & Co. Occlusive Peripheral Arterial Disease, The Merck Manual Home Health Handbook website, revised and updated March 2010. Retrieved March 4, 2012.
  4. 1 2 "Chronic Limb-Threatening Ischemia (CLTI) – Vascular Cures". Archived from the original on 2021-10-29. Retrieved 2021-10-27.
  5. ↑ Zhai Y, Petrowsky H, Hong JC, et al: Ischaemia-reperfusion injury in liver transplantation—From bench to bedside. Nat Rev Gastroenterol Hepatol 2013; 10:79–89
  6. ↑ Perico N, Cattaneo D, Sayegh MH, et al: Delayed graft function in kidney transplantation. Lancet 2004; 364:1814–1827
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  13. ↑ "Ischemic colitis - Symptoms and causes". Mayo Clinic. Retrieved 2021-10-27.
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  16. ↑ Kuźma, Elżbieta; Lourida, Ilianna; Moore, Sarah F.; Levine, Deborah A.; Ukoumunne, Obioha C.; Llewellyn, David J. (August 2018). "Stroke and dementia risk: A systematic review and meta-analysis". Alzheimer's & Dementia. 14 (11): 1416–1426. doi:10.1016/j.jalz.2018.06.3061. hdl:2027.42/152961. ISSN   1552-5260. PMC   6231970 . PMID   30177276. Archived from the original on 2021-08-28. Retrieved 2018-09-07.
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  23. ↑ Munshi, Raj; Hsu, Christine; Himmelfarb, Jonathan (2011-02-02). "Advances in understanding ischemic acute kidney injury". BMC Medicine. 9 (1): 11. doi: 10.1186/1741-7015-9-11 . ISSN   1741-7015. PMC   3038966 . PMID   21288330.
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