Ischemia

Ischemia is a restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism (to keep tissue alive).^[1] Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue. It also means local anemia in a given part of a body sometimes resulting from congestion (such as vasoconstriction, thrombosis or embolism). Ischemia comprises not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolites. The word is from Greek ἴσχαιμος iskhaimos, "staunching blood" from ἴσχω iskhο, "keep back, restrain" and αἷμα haima, "blood".

Signs and symptoms

Video explaining ischemia

Since oxygen is carried to tissues in the blood, insufficient blood supply causes tissue to become starved of oxygen. In the highly aerobic tissues of the heart and brain, irreversible damage to tissues can occur in as little as 3–4 minutes at body temperature. The kidneys are also quickly damaged by loss of blood flow. Tissues with slower metabolic rates may undergo irreversible damage after 20 minutes.

Clinical manifestations of acute limb ischemia (which can be summarized as the "six P's") include pain, pallor, pulseless, paresthesia, paralysis, and poikilothermia.^[2]

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.^[3]

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, which is the long-term accumulation of cholesterol-rich plaques in the coronary arteries. Ischemic heart disease is the most common cause of death in most Western countries and a major cause of hospital admissions.^[4]

Bowel

Both large and small bowel can be affected by ischemia. Ischemia of the large intestine may result in an inflammatory process known as ischemic colitis. Ischemia of the small bowel is called mesenteric ischemia.

Brain

Brain ischemia is insufficient blood flow to the brain, and can be acute or chronic. Acute ischemic stroke is a neurologic emergency that may be reversible if treated rapidly. Chronic ischemia of the brain may result in a form of dementia called vascular dementia. A brief episode of ischemia affecting the brain is called a transient ischemic attack (TIA), often erroneously referred to as a "mini-stroke".

Limb

Lack of blood flow to a limb results in acute limb ischemia.

Cutaneous

Reduced blood flow to the skin layers may result in mottling or uneven, patchy discoloration of the skin

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 atherosclerosis 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.^[3]

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).^[3]

• 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 or as a result of iatrogenic arterial injury (e.g., after angiography).^[3]

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)
• Hypotension (low blood pressure, e.g. in septic shock, 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-forces 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 can 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.

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 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 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.^[5]

Treatment

Early treatment is essential to keep the affected limb viable. The treatment options include injection of an anticoagulant, thrombolysis, embolectomy, surgical revascularisation, or amputation. Anticoagulant therapy is initiated to prevent further enlargement of the thrombus. Continuous IV unfractionated heparin has been the traditional agent of choice.^[3]

If the condition of the ischemic limb is stabilized with anticoagulation, recently formed emboli may be treated with catheter-directed thrombolysis using intraarterial 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.^[3]

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.^[3]

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.

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.^[6]

See also

• Cerebral ischemia
• Infarction
• Inhibitor protein
• Ischemic cascade
• Renal ischemia
• Reperfusion injury
• Trauma triad of death

References

Bibliography

• Elizabeth (editor). Oxford Reference: Concise Medical Dictionary (1990, 3rd ed.). Oxford University Press: Market House Books, 1987, 2nd ed., pg. 107, ISBN 0-19-281991-7, ISBN 978-0-19-281991-8