These projections are inhibitory and have been found to utilize both GABA and substance P. The indirect pathway, which projects to the globus pallidus external (GPe), is also inhibitory and uses GABA and enkephalin. The GPe projects to the subthalamic nucleus (STN), which then projects back to the GPi and GPe via excitatory, glutaminergic pathways. Excitation of the direct pathway leads to disinhibition of the GABAergic neurons of the GPi/SNr, ultimately resulting in activation of thalamic neurons and excitation of cortical neurons. In contrast, activation of the indirect pathway stimulates the inhibitory striatal GABA/enkephalin projection, resulting in suppression of GABAergic neuronal activity. This, in turn, causes disinhibition of the STN excitatory outputs, thus triggering the GPi/SNr inhibitory projections to the thalamus and decreased activation of cortical neurons. While deregulation of either of these pathways can disturb motor output, hyperkinesia is thought to result from overactivity of the direct pathway and decreased activity from the indirect pathway.Hyperkinesia occurs when dopamine receptors, and norepinephrine receptors to a lesser extent, within the cortex and the brainstem are more sensitive to dopamine or when the dopaminergic receptors/neurons are hyperactive. Hyperkinesia can be caused by a large number of different diseases including metabolic disorders, endocrine disorders, heritable disorders, vascular disorders, or traumatic disorders.
Unstable angina (UA), also called crescendo angina, is a type of angina pectoris that is irregular. It is also classified as a type of acute coronary syndrome (ACS).It can be difficult to distinguish unstable angina from non-ST elevation (non-Q wave) myocardial infarction (NSTEMI). They differ primarily in whether the ischemia is severe enough to cause sufficient damage to the hearts muscular cells to release detectable quantities of a marker of injury (typically troponin T or troponin I). Unstable angina is considered to be present in patients with ischemic symptoms suggestive of an ACS and no elevation in troponin, with or without ECG changes indicative of ischemia (e.g., ST segment depression or transient elevation or new T wave inversion). Since an elevation in troponin may not be detectable for up to 12 hours after presentation, UA and NSTEMI are frequently indistinguishable at initial evaluation. Signs and symptoms
Pathophysiology
The pathophysiology of unstable angina is controversial. Until recently, unstable angina was assumed to be angina pectoris caused by disruption of an atherosclerotic plaque with partial thrombosis and possibly embolization or vasospasm leading to myocardial ischemia. However, sensitive troponin assays reveal rise of cardiac troponin in the bloodstream with episodes of even mild myocardial ischemia. Since unstable angina is assumed to occur in the setting of acute myocardial ischemia without troponin release, the concept of unstable angina is being questioned with some calling for retiring the term altogether.