1 / 26

Diabetes mellitus complications & morphology

Diabetes mellitus complications & morphology. Complications of diabetes. In type 1 &2 diabetes Variable onset, severity ,organs of involvement Macrovascular disease: Accelerated atherosclerosis-MI,CVA,gangrene of legs

jane-cunningham
Download Presentation

Diabetes mellitus complications & morphology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Diabetes mellituscomplications & morphology

  2. Complications of diabetes • In type 1 &2 diabetes • Variable onset, severity ,organs of involvement • Macrovascular disease: Accelerated atherosclerosis-MI,CVA,gangrene of legs • Microvascular disease (microangiopathy)-retinopathy, nephropathy, neuropathy • Good control of blood glucose minimizes microangiopathy

  3. Pathogenesis • Metabolic derangements, hyperglycemia • Disease modifying elements ? Genetic • 3 probable pathways • Non enzymatic glycosylation:Formation of advanced glycosylation end products (AGE) • Activation of protein kinase C (PKC ) • Intracellular hyperglycemia with disturbances in polyol pathways

  4. Advanced Glycosylation End products(AGE ) • Non enzymatic reaction between *intracellular glucose-derived precusors & *Amino group of intracellular & extracellular proteins Have chemical & biological detrimental effects on extracellular matrix components & target cells of diabetic complications eg endothelial cells

  5. AGE effect on extracellular matrix components • On collagen & laminin • Cross linkage of polylpeptides –abn matrix-matrix or matrix cell linkages • Resistant to proteolytic digestion • Trap non-glycated plasma or interstitial proteins

  6. AGE Effects on Circulating plasma proteins • Generation of cytokines growth factors & pro inflammatory molecules eg insulin like growth factor,TGF β, PDGF,VEGF. • ↑ endothelial permeability • ↑ procoagulant activity • ↑proliferation & synthesis of ECM by fibroblasts & smooth muscle cells

  7. Activation of protein kinase C • Intracellular hyperglycemia causes de-novo synthesis of DAG from glycolytic intermediates & then activation of PKC (Normally by Ca) • Production of VEGF—endothelial &smooth muscle proliferation • ↑ activity of endothelin 1 (vasoconstrictor) • ↓ activity of endothelial NO synthase (vasodilator )-- ↑ microvascular contractility

  8. Intracellular hyperglycemia disturbances in polyol pathways • Hyperglycemia-------------sorbitol--fructose • Aldose reductase-cofactor NADPH • NADPH also needed as cofactor by glutathione reductase to produce reduced glutathione (GSH)-antioxidant • ↑ susceptibility to oxidative stress • Sorbitol may be directly toxic to cells Excessive reactive oxygen species

  9. Complications of DM • Acute metabolic complications DKA, hyperosmolar non ketotic coma,hypoglycemia • Late systemic complications; Macrovascular ,microangoipathy

  10. Macrovascular disease • Accelerated atherosclerosis of aorta & large and medium sized arteries • Myocardial infarction (women & men) • Gangrene of lower limbs • Hyaline arteriosclerosis associated with hypertension

  11. Diabetic microangiopathy • Diffuse thickening of basement membranes (but it is leaky) • Concentric layers of type IV collagen

  12. Diabetic nephropathy • Clinical syndromes • Asymptomatic proteinuria • Nephrotic syndrome • Progressive renal failure • Hypertension • End stage renal failure

  13. Diabetic nephropathy (cont.) • Diabetic glomerulosclerosis:Diffuse glomerulosclerosis:inv all parts of glomerulus • Thickening of GBM &diffuse increase in mesangial matrix and mesangial cells • Capsular drop, • Fibrin cap • Nodular glomerulosclerosis (Kimmelstiel –Wilson lesion)-PAS +,nodule, contain mesangial cells, pathognomonic of DM

  14. Diabetic nephropathy (cont) • Renal vessel atherosclerosis, • Hyaline arteriolosclerosis (afferent & efferent) • Chr Pyelonephritis,necrotizing papillitis • Tubular lesions Armanii Ebstein lesions

  15. Ocular: retinopathy (background non proliferative ,proliferative ),cataract glaucoma • Neuropathy:sensorimotor / autonomic

  16. DKA

  17. Pregnancy • Infants of diabetic mothers • Large for date • Hyperplasia of β cells of islet of Langerhan ---hypoglycemia • 5-10% risk of developmental abn of heart; neural tube defects.

More Related