Explain What Critical Events In Ischemic Cascade

Since glucose cannot enter the cells it builds up in the blood and the body's cells literally starve to death. Also since the body lacks sufficient energy from tissue glucose it begins to break down stored fat that produces ketenes, a byproduct of broken down fat, that makes the body's blood acidic interfering with respiration. About 700,000 people in the United States have Type I diabetes. Its symptoms are unusual thirst, frequent urination, extreme hunger, dramatic weight loss, fatigue, and irritability. If the disease is undetected or not properly treated it can quickly become fatal. Death by diabetic coma was usually the outcome of the disease before insulin was discovered.

A multitude of organs and body systems are affected by this disorder. When the demand for oxygen delivery from the blood exceeds the available blood supply for a particular organ, the organ becomes ischemic. Increased perfusion to the brain, kidneys and other major organs can cause them to fail. As time progresses all of the body’s systems are impaired in one way or another. [Medicinenet (2009) p2]

The average duration of a TIA is said to be a few minutes, however, it this has recently been corrected. By definition a transient ischemic attack could have symptoms that last up to a maximum of 24 hours.

The prolonged excitatory activation of ionotropic N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors as well as metabotropic glutamate receptor lead to neuronal cell death (Caccamo et al., 2004, Park et al., 2004). It is commonly accepted that ionotropic glutamate receptors are responsible for the harmful effect of excitotoxicity. The continued binding of excess glutamate to NMDA receptor induces the uncontrolled influx of calcium ions (Ca2+). This massive overload of intracellular Ca2+ leads to activation of calpain and mitochondrial oxidative phosphorylation which ultimately causes apoptosis (Caccamo et al., 2004, Choi, 1992, Lawson and Lowrie, 1998). The AMPA receptor is involved in regulating the influx of sodium ions (Na+). The continued activation of AMPA receptors, due to the unwarranted glutamate level, induces influx of Na+ which consequently leads to osmotic imbalance and swelling of the neurons (Caccamo et al., 2004). The excess swelling of neurons can leads to necrosis (Park et al., 2004). Consider as a therapeutic target, extracellular glutamate concentrations increase to neurotoxic levels within the first three hours after the injury (Liu et al., 1999, Liu and Bilkey, 1999, McAdoo et al., 1999), leaving a small time window for immediate treatment to prevent

1 out of 100 people in the U.S are affected with ischemic heart disease. Ischemic heart disease is also known as ischemic cardiomyopathy and is commonly caused by atherosclerosis. Atherosclerosis occurs when the inner layer of coronary artery is hardened due to buildups of cells.

Most of the current focus on developing neuroprotective therapies is aimed at preventing neuronal death. However, these approaches have not been successful despite many years of clinical trials mainly because the numerous side effects observed in humans and absent in animals used at preclinical level. Recently, the research in this field aims to overcome this problem by developing strategies which induce, mimic, or boost endogenous protective responses and thus do not interfere with physiological neurotransmission.

Ischemia-reperfusion (I/R) is a major cause of acute kidney injury (AKI). Ischemic AKI greatly contributes to patient morbidity and mortality in various clinical settings such as cardiac surgery and renal transplantation.1 Transplanted organs struggle with ischemia and subsequent reperfusion but also require pharmacological strategies to prevent graft rejection. Therefore immunosuppressive substances e.g. mTOR inhibitors had to be used in addition. Nevertheless, an effective therapy of ischemic AKI is still lacking. Ischemic preconditioning (IPC) is an intriguing phenomenon since it indicates the existence of intrinsic mechanisms that may be targeted for rendering the kidney resistant to ischemic stress. IPC can be achieved by pretreating the kidney itself (local IPC) or a remote organ (remote IPC). The conditioning stimulus may consist of one or several brief I/R cycles. This maneuver confers resistance against I/R injury upon subsequent long-lasting ischemia (“index ischemia”). IPC-mediated renoprotection occurs within the so-called early (minutes to few hours after IPC) and late windows of protection (24 hours to several days after IPC).

It will damage the brain by a protein which will abnormally form amyloid plaques and tan tangles. The damages to the brain probably exist more than 10 years before cognitive problems occur which means it is symptom-free during preclinical stage. At beginning, damage happens in hippocampus, affects the forming of memories. Then, after more neuron is died and more parts of brain are affected, the brain began to shrink. Lastly, damage spreads widely and the shrinkage can be seen obviously.

As we have learned during our anatomy and physiology courses, our bodies produce more adenosine triphosphate in the presence of oxygen. When oxygen is not restored and the hypoxic injury continues, there is not enough ATP to remove the calcium from the cytosol and the calcium pump fails, which causes an increase of cytosolic calcium concentration (Huether & McCance, 2012, p. 83). This accumulation of calcium in the cytoplasm will trigger the activation of several enzyme systems ¨resulting in membrane damage, cytoskeleton disruption, DNA and chromatin degradation, ATP depletion, and actual cell death¨ (Huether & McCance, 2012, p. 65).

When the situation is serious and an acute ischemia is life-threatening, signals are quite different:

becomes deprived of oxygen. Also, with a lot of plaque buildup in the arteries, the arteries could rupture and force the body to have a heart attack. Coronary Heart disease is the number one killer of men and women in the united state (“coronary…”)!

If the metabolic needs of the tissue are insufficiently met due to a possible perfusion to a segment of intestine and unless the process is interrupted, occurrence of ischemia will appear, which will in the end, lead to necrosis and

Nuclear factor kappa b (NF-κB) and tumor necrosis factor-α (TNF-α) induce oxidative stress and apoptosis in many cell types also cytokines and inflammatory mediators may participate to cause excitotoxic and apoptotic neuronal death.

The involvement of intracellular Ca2+ may be the underlying mechanism of these functional disorders. It is likely that endoplasmic reticulum disturbances are partially responsible for increasing the risk of cell death. Oxygen radicals play a part in the microvascular and parenchymal cell injury which are affiliated with organ preservation. Oxygen radicals seem to create large leakages mainly in the small venules and thus increase microvascular permeability. The hydroxyl radical, which is highly reactive, seems to be the cause of the oxygen radical production-associated microvascular alterations. While many other similar types of cell injury are triggered by an enhanced released of 02- (superoxide anion radical) or H2O2 (hydrogen peroxide), cold-induced cell injury is not. Rather, an increase in the redox-active, cellular chelatable iron pool that transforms species with low reactivity into those that are highly

After about 4 minutes without blood and oxygen, brain cells become damaged and may die. The body tries to restore blood and oxygen to the cells by enlarging other blood vessels (arteries) near the area.