Download MBBS Pathology PPT 6 Pathological Changes In Diabetes Mellitus Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Pathology PPT 6 Pathological Changes In Diabetes Mellitus Lecture Notes

Pathological Changes in Diabetes

Mel itus

? Pancreas
? Diabetic Nephropathy
? Diabetic Cardiomyopathy
? Diabetic Retinopathy
? Diabetic Neuropathy


Four distinct mechanisms

1-Formation of Advanced Glycation End Products. Advanced glycation

end products (AGEs) are formed as intracellular

glucose derived dicarbonyl precursors+ amino groups

advanced glycation end product(AGEs)
(glyoxal, methylglyoxal, and 3-deoxyglucosone)


? AGEs bind to a specific receptor (RAGE) that is expressed on

inflammatory cells (macrophages and T cells), endothelium, and

vascular smooth muscle.

AGE-RAGE signal ing axis

? TGF-excess basement membrane material
? vascular endothelial growth factor (VEGF)- neovasculerization
? reactive oxygen species (ROS) in endothelial cells
? procoagulant activity
? Enhanced proliferation of vascular smooth muscle cells and synthesis

of extracellular matrix
2-Activation of Protein Kinase C.
second messenger diacyl glycerol (DAG) is an important signal

transduction pathway.
Intracellular hyperglycemia--- de novo synthesis of DAG--excessive

PKC activation- vascular permeability and angiogenesis

3-Oxidative Stress and Disturbances in Polyol Pathways

? Sustained hyperglycemia---- aldol reductase-- progressive depletion of

intracellular NADPH -- decreased rgeneration of reduced

glutathione(GSH) - increasing cellular susceptibility to oxidative

stress
4-Hexosamine Pathways and Generation of Fructose-6- Phosphate
Hyperglycemia ---increases intracellular levels of fructose-6-
phosphate via HM- excess proteoglycans - abnormal
expression of TGF or PAI-1--- exacerbate the end-organ damage

Pancreas

Pancreatic Islets-
1-Insulitis:
? In type 1 DM-
?lymphocytic infiltrate,macrophage and few polymorphs
? In type 2 DM-
?variable degree of fibrous tissue in the islets


2-Islet cell mass:
? Type-1- loss of pancreatic -cells and its hyalinisation
? In type 2 DM-hyperplasia and hypertrophy of islets
3-Amyloidosis:
? type 1 DM- absent
? Type-2DM-around the capillaries of the islets causing compression

and atrophy of islet tissue


Diabetic Nephropathy

Nephrosclerosis


Pathogenesis in Diabetic nephropathy






Diabetic Retinopathy







Intra retinal microangiopathy (IRMA)(NPDR)


Neovascularization

Diabetic Cardiomyopathy



Diabetic Neuropathy