Diabetes Mellitus And Renal Hypoxia Essay

1024 words - 5 pages

i. Inadequate oxygenation of the blood in the lungs because of extrinsic reasons.
a) deficiency of O2 in the atmosphere.
b) Hypoventilation.
ii. Pulmonary diseases.
a) Hypoventilation caused by increased alveolar resistance or decreased pulmonary compliance.
b) Abnormal alveolar ventilation/ perfusion.
c) Diminish respiratory membrane diffusion.
iii. Venous to atrial shunt.
iv. Inadequate O2 transport to the tissues by the blood.
a) Anemia or abnormal hypoventilation
b) General circulatory deficiency.
c) Localized circulatory deficiency.
d) Tissue edema.
v. Inadequate tissue capability of using oxygen.
a) Poisoning of cellular oxidation enzymes.
b) Diminish ...view middle of the document...

In addition to that, diabetes nephropathy is stron gly associated with increased oxidative stress and kidney tissue hypoxia. The increased oxidative stress causes increased oxygen consumption resulting in kidney tissue hypoxia.

Adaptation to hypoxia
Oxygen deprivation is an important determinant of cellular function. The role of hypoxia-inducible factors (HIFs) in O2 supply and adaptation to hypoxic conditions has a greater effect in increasing support. HIFs are O2-sensitive transcription factors which are involved in O2-dependent gene regulation that mediates cellular adaptation to O2 deprivation and tissue protection under hypoxic conditions in the kidney.
HIF is not degraded, under hypoxic conditions but instead accumulates in the cytoplasm and induces transcription of target genes after binding to a hypoxia-response element following translocation into the nucleus. However, NO may reduce the activation of HIF in hypoxia via the inhibitory effect of NO on cytochrome oxidase enzyme. Therefore, it seems that NO has a considerable effect on HIF expression. HIF-1α up regulates a number of factors implicated in angiogenic growth factors—such as vascular endothelial growth factor (VEGF), endothelial progenitor cell recruitment via the endothelial expression of SDF-1, hemeoxygenase 1 (HO-1), and erythropoietin (EPO and vasomotor regulation. Endothelial cell proliferation and differentiation, increase vascular permeability, and mediate endothelium-dependent vasodilation can be stimulated by vascular endothelial growth factors.

HIF may also be involved in potentially deleterious responses to renal hypoxia, including the promotion of fibrosis. The precise role of HIF in hypoxia is induction of cell death and HIF has also been implicated in regulating apoptotic and cell death pathways.
Inter- and intracell type differences exist in the ability of cells to induce HIF activity in response to systemic hypoxia. In the kidney, expression of hypoxia inducible factors are variable according to the cell type.HIF-1α is expressed in tubular cells, whereas HIF-2 α is expressed in peritubular cells, renal interstitional fibroblasts and endothelial cells.

Effects of renal hypoxia

1. Regulation of erythropoiesis by hypoxia
Human EPO is heavily glycosylated structure, consists of 165 amino acids and has a molecular mass of about 30 kDa, 40% of which is derived from its carbohydrate component. The...

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