Iron pathophysiology

Parkinson s disease 253-4, 298 pathophysiology of iron in humans 228 absorption disorders 211-20 acquired and genetic disorders 207 deficiency... 

In this chapter we will focus on pathophysiological aspects of iron deficiency and iron overload, describing functional relations between cells and organs as a link between biochemistry and medicine. Clinical, diagnostic and therapeutic aspects will only be mentioned if particularly relevant for pathophysiology. 

Main pathophysiological mechanisms of iron loading that may result in an infectious risk 1.1 Increased gastrointestinal absorption of iron I.2a Parenteral administration of iron I.2b Increased release of iron in the blood stream (haemolysis) 1.3 Increased inhalation of iron II Chronic inflammation III Diabetic ketoacidosis increased... 

Boelaert, J.R., Pootrakul, P., Chaiprasert, A., Van Landuyt, H.W., Lambert, A. and Winkel-mann, G. (1999s). Pathophysiology of pythiosis in thalassemic patients. Abstracts of the World Congress of Iron Metabolism Bioiron 99, Sorrento, May 23-28, abstr. p. 372. 

It has also been shown that LDL oxidation is increased in diabetes. In this connection, Mowri et al. [179] studied the effect of glucose on metal ion-dependent and -independent LDL oxidation. They found that pathophysiological glucose concentrations enhanced copper- and iron-induced LDL oxidation measured via the formation of conjugated dienes. In contrast, glucose had no effect on metal-independent free radical LDL oxidation. Correspondingly,... 

At present, many natural and synthetic chelators have been studied as potential pharmacological agents for the treatment of iron or copper overload under various pathophysiological conditions. (The chelating activity of flavonoids was already discussed above and the application of chelators in thalassemia and some other pathologies is considered in Chapter 31.) There are specific thermodynamic demands to chelators to be efficient antioxidants [369], We will consider just several chelators of potential therapeutic importance. 

Pathophysiologically, the normal red cell mass, reflected in haemoglobin level or packed cell volume, decreases in anaemia. The mandatory first step is to identify the cause for this change and correct it, wherever possible, prior to initiating treatment. It makes little sense only to replace iron in a patient who continues to rapidly loose blood from the gastrointestinal tract due to a heavy hookworm infestation or a resectable carcinoma of the caecum. Accordingly, it will be assumed throughout that a... 

Pathophysiologically normochromic and normo-cytic anaemia, as occurs in many clinical syndromes exemplified by renal failure, a number of cancers, rheumatoid arthritis and systemic lupus erythematosus, is typical. Initially erythrocytes are of normal size and degree of haemoglobinization. However, persistent impairment of iron supply, especially from mitochondria to globin in the cytoplasm, leads to them becoming hypochromic and microcytic. 

Different classifications of anemia are based in part on the pathophysiological factor inducing the decreased hemoglobin concentration. Anemias due to cell hy-poproliferation include aplastic anemia and iron deficiency anemia. Hemolytic anemia results from excessive destruction of red blood cells. Megaloblastic anemia, sideroblastic anemia, and iron deficiency anemia result from an abnormality in the maturation of red blood cells. 

Bipolar disorder, once known as manic-depressive illness, was conceived of as a psychotic disorder distinct from schizophrenia at the end of the 19th century. Before that both of these disorders were considered part of a continuum. It is ironic that the weight of the evidence today is that there is profound overlap in these disorders. This is not to say that there are no pathophysiologically important differences or that some drug treatments are differentially effective in these disorders. According to DSM-IV, they are separate disease entities while research continues to define the dimensions of these illnesses and their genetic and other biological markers. 

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