The major cause of acute limb ischaemia is arterial thrombosis (85%), while embolic occlusion is responsible for 15% of cases. In rare instances, arterial aneurysm of the popliteal artery has been found to create a thrombosis or embolism resulting in ischaemia.

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).

When a limb is ischemic in the non-acute (chronic) setting, the condition is alternatively called peripheral artery disease or critical limb ischemia, rather than ALI. In addition to limb ischemia, other organs can become ischemic, causing:

- Renal ischemia (nephric ischemia)

- Mesenteric ischemia

- Cerebral ischemia

- Cardiac ischemia

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).

- Thromboembolism (blood clots)

- Embolism (foreign bodies in the circulation, e.g. amniotic fluid embolism)

70% of patients with carotid arterial dissection are between the ages of 35 and 50, with a mean age of 47 years.

With treatment, approximately 80% of patients are alive (approx. 95% after surgery) and approximately 70% of infarcted limbs remain vital after 6 months.

Non-occlusive disease has a poor prognosis with survival rate between 40-50%.

The major tissues affected are nerves and muscles, where irreversible damage starts to occur after 4–6 hours of cessation of blood supply.Skeletal muscle, the major tissue affected, is still relatively resistant to infarction compared to the heart and brain because its ability to rely on anaerobic metabolism by glycogen stored in the cells may supply the muscle tissue long enough for any clot to dissolve, either by intervention or the body's own system for thrombus breakdown. In contrast, brain tissue (in cerebral infarction) does not store glycogen, and the heart (in myocardial infarction) is so specialized on aerobic metabolism that not enough energy can be liberated by lactate production to sustain its needs.

Bone is more susceptible to ischemia, with hematopoietic cells usually dying within 2 hours, and other bone cells (osteocytes, osteoclasts, osteoblasts etc.) within 12–20 hours. On the other hand, it has better regenerative capacity once blood supply is reestablished, as the remaining dead inorganic osseous tissue forms a framework upon which immigrating cells can reestablish functional bone tissue in optimal conditions.

CT angiography would be helpful in differentiating occlusive from non-occlusive causes of mesenteric ischaemia.

Once considered uncommon, spontaneous carotid artery dissection is an increasingly recognised cause of stroke that preferentially affects the middle-aged.

The incidence of spontaneous carotid artery dissection is low, and incidence rates for internal carotid artery dissection have been reported to be 2.6 to 2.9 per 100,000.

Observational studies and case reports published since the early 1980s show that patients with spontaneous internal carotid artery dissection may also have a history of stroke in their family and/or hereditary connective tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome, autosomal dominant polycystic kidney disease, pseudoxanthoma elasticum, fibromuscular dysplasia, and osteogenesis imperfecta type I. IgG4-related disease involving the carotid artery has also been observed as a cause.

However, although an association with connective tissue disorders does exist, most people with spontaneous arterial dissections do not have associated connective tissue disorders. Also, the reports on the prevalence of hereditary connective tissue diseases in people with spontaneous dissections are highly variable, ranging from 0% to 0.6% in one study to 5% to 18% in another study.

Internal carotid artery dissection can also be associated with an elongated styloid process (known as Eagle syndrome when the elongated styloid process causes symptoms).

Major risk factors for cerebral infarction are generally the same as for atherosclerosis: high blood pressure, Diabetes mellitus, tobacco smoking, obesity, and dyslipidemia. The American Heart Association/American Stroke Association (AHA/ASA) recommends controlling these risk factors in order to prevent stroke. The AHA/ASA guidelines also provide information on how to prevent stroke if someone has more specific concerns, such as Sickle-cell disease or pregnancy. It is also possible to calculate the risk of stroke in the next decade based on information gathered through the Framingham Heart Study.

Risk factors contributing to PAD are the same as those for atherosclerosis:

- Smoking – tobacco use in any form is the single most important modifiable cause of PAD internationally. Smokers have up to a tenfold increase in relative risk for PAD in a dose-response relationship. Exposure to second-hand smoke from environmental exposure has also been shown to promote changes in blood vessel lining (endothelium) which is a precursor to atherosclerosis. Smokers are 2 to 3 times more likely to have lower extremity peripheral arterial disease than coronary artery disease. More than 80%-90% of patients with lower extremity peripheral arterial disease are current or former smokers. The risk of PAD increases with the number of cigarettes smoked per day and the number of years smoked.

- Diabetes mellitus – causes between two and four times increased risk of PAD by causing endothelial and smooth muscle cell dysfunction in peripheral arteries. The risk of developing lower extremity peripheral arterial disease is proportional to the severity and duration of diabetes.

- Dyslipidemia – a high level of low-density lipoprotein (LDL cholesterol) and a low level of high-density lipoprotein (HDL cholesterol) in the blood) - elevation of total cholesterol, LDL cholesterol, and triglyceride levels each have been correlated with accelerated PAD. Correction of dyslipidemia by diet and/or medication is associated with a major improvement in rates of heart attack and stroke.

- Hypertension – elevated blood pressure is correlated with an increase in the risk of developing PAD, as well as in associated coronary and cerebrovascular events (heart attack and stroke). Hypertension increased the risk of intermittent claudication 2.5- to 4-fold in men and women, respectively.

- Risk of PAD also increases in individuals who are over the age of 50, male, obese, heart attack, or stroke or with a family history of vascular disease.

- Other risk factors which are being studied include levels of various inflammatory mediators such as C-reactive protein, fibrinogen, hyperviscosity, hypercoagulable state.

Most commonly, intermittent (or vascular or arterial) claudication is due to peripheral arterial disease which implies significant atherosclerotic blockages resulting in arterial insufficiency. It is distinct from neurogenic claudication, which is associated with lumbar spinal stenosis. It is strongly associated with smoking, hypertension, and diabetes.

Peripheral arterial disease is more common in the following populations of people:

- All people who have leg symptoms with exertion (suggestive of claudication) or ischemic rest pain.

- All people aged 65 years and over regardless of risk factor status.

- All people between the age of 50 to 69 and who have a cardiovascular risk factor (particularly diabetes or smoking).

- Age less than 50 years, with diabetes and one other atherosclerosis risk factor (smoking, dyslipidemia, hypertension, or hyperhomocysteinemia).

- Individuals with an abnormal lower extremity pulse examination.

- Those with known atherosclerotic coronary, carotid, or renal artery disease.

- All people with a Framingham risk score 10%-20%

- All people who have previously experienced chest pain

Intermittent claudication (Latin: "claudicatio intermittens") is a symptom that describes muscle pain on mild exertion (ache, cramp, numbness or sense of fatigue), classically in the calf muscle, which occurs during exercise, such as walking, and is relieved by a short period of rest. It is classically associated with early-stage peripheral artery disease, and can progress to critical limb ischemia unless treated or risk factors are modified.

Claudication derives from the Latin verb "claudicare", "to limp".

While some investigations suggest a possible beneficial effect of mesenchymal stem cells on heart and kidney reperfusion injury, to date, none have explored the role of stem cells in muscle tissue exposed to ischemia-reperfusion injury.

Stem cells have been implicated in the regeneration of skeletal muscle after traumatic and blast injuries, and have been shown to hone to muscle damaged after exercise.

Serum lactate level is a proxy measure of tissue oxygenation. When tissues do not have adequate oxygen delivery (i.e., are ischemic), they revert to less efficient metabolic processes, producing lactic acid.

Myoglobin is released from damaged muscle, as in the case of ischemia.

Serum creatinine and BUN may be elevated in the setting of Acute Kidney Injury.

Whether a cerebral infarction is thrombotic or embolic based, its pathophysiology, or the observed conditions and underlying mechanisms of the disease. In thrombotic ischemic stroke, a thrombus forms and blocks blood flow. A thrombus forms when the endothelium is activated by a variety of signals to result in platelet aggregation in the artery. This clump of platelets interacts with fibrin to form a platelet plug. This platelet plug grows into a thrombus, resulting in a stenotic artery. Thrombotic ischemia can occur in large or small blood vessels. In large vessels, the most common causes of thrombi are atherosclerosis and vasoconstriction. In small vessels, the most common cause is lipohyalinosis. Lipohyalinosis is when high blood pressure and aging causes a build-up of fatty hyaline matter in blood vessels. Atheroma formation can also cause small vessel thrombotic ischemic stroke.

An embolic stroke refers to the blockage of an artery by an embolus, a traveling particle or debris in the arterial bloodstream originating elsewhere. An embolus is most frequently a thrombus, but it can also be a number of other substances including fat (e.g. from bone marrow in a broken bone), air, cancer cells or clumps of bacteria (usually from infectious endocarditis). The embolus may be of cardiac origin due to Atrial fibrillation, Patent foramen ovale or from atherosclerotic plaque of another (or the same) large artery. Cerebral artery gas embolism (e.g. during ascent from a SCUBA dive) is also a possible cause of infarction (Levvett & Millar, 2008)

Functional hyperaemia is an increase in blood flow to a tissue due to the presence of metabolites and a change in general conditions. When a tissue increases activity there is a well-characterized fall in the partial pressure of oxygen and pH, an increase in partial pressure of carbon dioxide, and a rise in temperature and the concentration of potassium ions. The mechanisms of vasodilation are predominantly local metabolites and myogenic effects. Increased metabolic activity of the tissue leads to a local increase in the extracellular concentration of such chemicals as adenosine, carbon dioxide, and lactic acid, and a decrease in oxygen and pH. These changes cause significant vasodilation. The reverse occurs when metabolic activity is slowed and these substances wash out of the tissues. The myogenic effect refers to the inherent attempt of vascular smooth muscle surrounding arterioles and arteries to maintain the tension in the wall of these blood vessels by dilating when internal pressure is reduced and to constrict when wall tension increases.

Blue toe syndrome is a situation that may reflect atherothrombotic microembolism, causing transient focal ischaemia, occasionally with minor apparent tissue loss, but without diffuse forefoot ischemia. The development of blue or violaceous toes can also occur with trauma, cold-induced injury, disorders producing generalized cyanosis, decreased arterial flow, impaired venous outflow, and abnormal circulating blood.

The terms "blue toe syndrome", "grey toe syndrome" and "purple toe syndrome" are sometimes used interchangeably.

Studies may include echocardiography, thoracic and abdominal CT or MRI, peripheral arterial run off imaging studies, hypercoagulopathy labs, and interrogation of syndromes that lead to peripheral vascular pathology.

Hyperaemia, hyperæmia, or hyperemia (Greek ὑπέρ (hupér, "over") + αἷμα (haîma, “blood”)) is the increase of blood flow to different tissues in the body. It can have medical implications but is also a regulatory response, allowing change in blood supply to different tissues through vasodilation. Clinically, hyperaemia in tissues manifest as erythema (redness of the skin) because of the engorgement of vessels with oxygenated blood. Hyperaemia can also occur due to a fall in atmospheric pressure outside the body.

While the exact incidence is unknown, estimates range from 33 - 57 percent of patients staying in the ICU for longer than 7 days. More exact data is difficult to obtain, since variation exists in defining the condition.

The three main risk factors for CIP and CIM are sepsis and systemic inflammatory response syndrome (SIRS), and multi-organ failure. Reported rates of CIP/CIM in people with sepsis and SIRS range from 68 to 100 percent. Additional risk factors for developing CIP/CIM include: female gender, high blood sugar (hyperglycemia), low serum albumin, and immobility. A greater severity of illness increases the risk of CIP/CIM. Such risk factors include: multi-organ dysfunction, renal failure, renal replacement therapy, duration of organ dysfunction, duration of ICU stay, low albumin, and central neurologic failure.

Certain medications are associated with CIP/CIM, such as corticosteroids, neuromuscular blocking agents, vasopressors, catecholamines, and intravenous nutrition (parenteral nutrition). Research has produced inconsistent results for the impact of hypoxia, hypotension, hyperpyrexia, and increased age on the risk of CIP/CIM. The use of aminoglycosides is "not" an independent risk for the development of CIP/CIM.

Thrombosis prevention is initiated with assessing the risk for its development. Some people have a higher risk of developing thrombosis and its possible development into thromboembolism. Some of these risk factors are related to inflammation. "Virchow's triad" has been suggested to describe the three factors necessary for the formation of thrombosis: stasis of blood, vessel wall injury, and altered blood coagulation. Some risk factors predispose for venous thrombosis while others increase the risk of arterial thrombosis.

In medicine, aortoiliac occlusive disease, also known as Leriche's syndrome and Leriche syndrome, is a form of central artery disease involving the blockage of the abdominal aorta as it transitions into the common iliac arteries.

Although strains are not restricted to athletes and can happen while doing everyday tasks, however, people who play sports are more at risk for developing a strain. It should also be noted that it is common for an injury to develop when there is a sudden increase in duration, intensity, or frequency of an activity.