Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many mechanisms contribute to the complex pathophysiology of sickle cell disease (SCD), with dysfunction of the vascular endothelium as a unifying theme. Specifically, hemolysis-associated low arginine and nitric oxide (NO) bioavailability, amplified by NO synthase uncoupling, elevated arginase activity, superoxide production, oxidative stress, accumulation of arginine analogs such as asymmetric dimethylarginine, ischemia-reperfusion injury, inflammation, apolipoprotein A-1 depletion, and a hypercoagulable state are significant mechanisms contributing to endothelial dysfunction. Genetic polymorphisms also influence disease severity. Clearly the variable spectrum of disease is the consequence of multiple events and genetic susceptibility that go beyond the occurrence of a single amino acid substitution in the beta globin chain of hemoglobin. Recent studies begin to demonstrate overlap among these seemingly unrelated processes. Impaired NO bioavailability represents the central feature of endothelial dysfunction, and is a common denominator in the pathogenesis of vasculopathy in SCD. The consequences of decreased NO bioavailability include endothelial cell activation, upregulation of the potent vasoconstrictor endothelin-1, vasoconstriction, platelet activation, increased tissue factor, and activation of coagulation, all of which ultimately translate into the clinical manifestations of SCD. Evidence supporting vasculopathy subphenotypes in SCD, including pulmonary hypertension, priapism, cutaneous leg ulceration, and stroke, will be reviewed and relevance to other hemolytic disorders including the thalassemia syndromes will be considered.
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PMID:Mechanisms of vasculopathy in sickle cell disease and thalassemia. 1907 78

The hemoglobin S is a consequence of the substitution of valine for glutamic acid at position 6 of beta globin chain. The problem arises when some individuals with Hb S is moved to the mountains and exposed to hypoxia. The decrease in oxygen saturation distorts the red blood cell with HbS-shaped crescent (sickle cell). Sickle cell (rigid and fragile) tends to adhere to the other red blood cells, generating a series of intravascular alterations that can lead to tissue ischemia or infarction. The spleen by type of movement and lack of lateral communications between the branches of the splenic artery was the most susceptible to sickle cell crisis. Splenic infarction at altitude corresponding to different circumstances can evolve in three stages: a) Acute (focal, uncomplicated), b) massive attack (more than 50% of parenchyma) and c) spontaneous rupture.Early diagnosis is crucial, allowing the quick and timely introduction of various measures, including adequate hydration and oxygenation continues until its evacuation to lower altitude locations. These measures would reduce the phenomenon of sickle and some patients may overcome this acute trance without major complications. The delay in diagnosis leads to action that can exacerbate tissue hypoxia and cause ischemia or infarction of various organs. A large population of black and mixed race of African descent living in the Peruvian coast, 10% and 2% respectively have hemoglobin S; Caucasian subjects with Mediterranean ancestry this hemoglobin also can carry. It is therefore essential to disseminate within the clinicians working in regions of high status and to thus prevent potentially fatal complications in patients with Hb S; is also essential to promote preventive measures for individuals with African or Mediterranean ancestry know their sickle cell status before traveling to places above 2,500 m.
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PMID:[Spleen infarction and S hemoglobinopathies S in the high altitude lands]. 2247 81