Mathematical model of hemodynamic mechanisms and consequences of glomerular hypertension in diabetic mice

Schematic representation of the base model of renal function. (Top Left) The renal vasculature is modeled by a single preafferent resistance vessel flowing into N parallel nephrons. Bottom Left) Na+ and water filtration through the glomerulus are modeled according to Starling’s law. Na+ and water are reabsorbed at different fractional rates in the proximal tubule, loop of Henle, distal convoluted tubule, and connecting tubule/collecting duct, and Na+ and water excretion rates are determined from unabsorbed Na+ and water. Top right) Na+ and water excretion feed into the cardiovascular portion of the model, where the balance between excretion and intake determines extracellular fluid volume, plasma Na+ concentration, cardiac output (CO) and ultimately mean arterial pressure (MAP). Na+ concentration and MAP feed back into the renal model (left), closing the loop. Bottom Right) Multiple regulatory mechanisms, including the renin-angiotensin-aldosterone system (RAAS), tubulo-glomerular feedback (TGF), myogenic autoregulation, renal interstitial hydrostatic pressure (RIHP) regulation of tubular Na+ reabsorption, vasopressin regulation of tubular water reabsorption, and local blood flow autoregulation, provide feedbacks on model variables, to maintain or return homeostasi