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 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.[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 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]
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]
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 or opioids, can result in ischemia of the extremities due to unusual body positions that prevent normal circulation
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.
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]
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]
^Merck & Co. Occlusive Peripheral Arterial Disease, The Merck Manual Home Health Handbook website, revised and updated March 2010. Retrieved March 4, 2012.
^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
^Perico N, Cattaneo D, Sayegh MH, et al: Delayed graft function in kidney transplantation. Lancet 2004; 364:1814–1827
^World Health Organization Department of Health Statistics and Informatics in the Information, Evidence and Research Cluster (2004). The global burden of disease 2004 update. Geneva: WHO. ISBN92-4-156371-0.
