The Physiology of the Glomerulus

Abstract Glomerular flow is key to renal function. Afferent and efferent arterioles move blood into and out of the glomerulus, and efferent arterioles also branch into peritubular capillaries, which provide nutrients and remove waste from neighboring glomeruli. Many mechanisms regulate pressure in these arterioles, including tubuloglomerular feedback (that responds to intratubular sodium chloride levels), and several important signaling molecules such as adenosine, angiotensin II, and paracrine agents released by endothelial cells. This regulation protects the kidney and controls filtration and diuresis under different physiologic conditions. Many common antihypertensives, including ACE inhibitors, loop diuretics, and calcium channel blockers, affect these regulatory pathways in addition to their systemic effects on blood pressure. Between the arterioles, the glomerular capillaries are the site where plasma moves across a filtration barrier into the urinary space. The glomerular filtration barrier filters molecules based on size and charge and is made of three types of filters: the endothelial fenestrations in glomerular capillaries, the glomerular basement membrane, and the visceral epithelial cell podocyte slit diaphragm. Injury at any of these layers can disrupt the filtration barrier and lead to proteins or blood cells entering Bowman's space as part of urine. Normally, this filtration barrier will pass water and small molecules freely, but filtration of larger molecules also happens. The traditional view that fluid entering the tubule from the glomerular capillaries is virtually protein free is being questioned. For example, albumin and other proteins of similar size are filtered partially and then reabsorbed inside the tubule and by proximal tubule epithelial cells using the megalin/cubilin complex.