Pathogenesis of diabetic microangiopathy. The hemodynamic view.
Multiple factors, including altered levels of vasoactive substances, altered vasomotor responsiveness, chronic plasma volume expansion, and tissue hypoxia, contribute to a state of generalized microvascular vasodilatation in early insulin-dependent diabetes mellitus. This vasodilatation, with the consequent elevation in capillary pressures and flows, may be the initiating mechanism leading to both renal and extrarenal diabetic microangiopathy. Sustained hemodynamic actions on the microvasculature, besides directly injuring the capillary wall, promote increased permeability to macromolecules and increased capillary wall proliferation, with consequent thickening of basement membranes and luminal narrowing. These changes eventuate in complete microvascular obstruction and further vasodilatation of less damaged capillaries, thereby ensuring their eventual destruction. The ensuing complications depend on the nature of the surrounding tissue, ranging from reduction of functional reserve, as seen in skeletal muscle, to the devastating functional consequences observed in organs with endarterial circulation such as the kidney and retina.
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D001794:Blood Pressure; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability; D002395:Catecholamines / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000098:blood supply; D008833:Microcirculation / Q000503:physiopathology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System; D012171:Retinal Vessels / Q000503:physiopathology; D014664:Vasodilation
D002395:Catecholamines; D011453:Prostaglandins; D011945:Receptors, Angiotensin; D000804:Angiotensin II