University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

67

Pages:

2
Author:

Mariam A.

Pathology of diabetic nephropathy   Pathologic abnormalities noted in patients with long-standing diabetes mellitus before onset of microalbuminuria. There are 3 major histologic changes in the glomeruli: o Mesangial expansion - increase in mesangial matrix and mild proliferation of mesangial cells o Glomerular basement membrane thickening o Glomerular sclerosis - often associated with hyaline deposits in the glomerular arterioles Below are two images comparing normal glomerulus (left) and a glomerulus affected by diabetic nephropathy (right): Pathogenesis of diabetic nephropathy  There are several different pathogenic processes involved in the mechanisms of diabetic nephropathy Glomerular hyperfiltration     Two main components to this mechanism: o Intraglomerular hypertension – responsible for the rise in GFR o Glomerular hypertrophy – increases shear stress on the glomerular capillary wall Note that the glomerular hypertrophy and increased renal size accompany the rise in GFR The glomerular hypertension is caused by the dilatation of the afferent glomerular arteriole, contributed by increasing intraglomerular pressure and increasing renal blood flow The reasons for these haemodynamic changes is not well understood, however the following factors may contribute: o Hormones: IGF-1, ANP and sex hormones all seem to contribute to renal vasodilation and glomerular hyperfiltration o Sorbitol: Aldose reductase converts intracellular glucose to sorbitol, which then accumulates within the cells. This sorbitol, as well as the formation of glycosylated proteins, appears to contribute to the rise of GFR observed in diabetic nephropathy o Enhanced tubular sodium reabsorption: Hyperinsulinaemia (due to regular administration) and mild hyperglycaemia stimulate Na + reabsorption via increased sodium-glucose co-transport in the proximal tubule. This activates the tubuloglomerular feedback in the macula densa, raising the GFR via dilatation of the afferent arteriole