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

Pathological Changes in Diabetes

Mel itus

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

Four distinct mechanisms

1-Formation of Advanced Glycation End Products. Advanced glycation

--- Content provided by FirstRanker.com ---

end products (AGEs) are formed as intracellular

glucose derived dicarbonyl precursors+ amino groups

--- Content provided by FirstRanker.com ---

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


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

--- Content provided by FirstRanker.com ---

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

vascular smooth muscle.

--- Content provided by FirstRanker.com ---

AGE-RAGE signal ing axis

? TGF-excess basement membrane material
? vascular endothelial growth factor (VEGF)- neovasculerization
? reactive oxygen species (ROS) in endothelial cells

--- Content provided by FirstRanker.com ---

? procoagulant activity
? Enhanced proliferation of vascular smooth muscle cells and synthesis

of extracellular matrix
2-Activation of Protein Kinase C.

--- Content provided by FirstRanker.com ---

second messenger diacyl glycerol (DAG) is an important signal

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

--- Content provided by FirstRanker.com ---

PKC activation- vascular permeability and angiogenesis

3-Oxidative Stress and Disturbances in Polyol Pathways

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

--- Content provided by FirstRanker.com ---

intracellular NADPH -- decreased rgeneration of reduced

glutathione(GSH) - increasing cellular susceptibility to oxidative

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

Pancreas

Pancreatic Islets-
1-Insulitis:

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

? type 1 DM- absent
? Type-2DM-around the capillaries of the islets causing compression

and atrophy of islet tissue

--- Content provided by FirstRanker.com ---

Diabetic Nephropathy

Nephrosclerosis

--- Content provided by FirstRanker.com ---

Pathogenesis in Diabetic nephropathy

--- Content provided by FirstRanker.com ---

Diabetic Retinopathy

--- Content provided by FirstRanker.com ---

--- Content provided by FirstRanker.com ---

Intra retinal microangiopathy (IRMA)(NPDR)


Neovascularization

--- Content provided by FirstRanker.com ---

Diabetic Cardiomyopathy

--- Content provided by FirstRanker.com ---

Diabetic Neuropathy