Chapter 21 - Biophysical Basis of Glomerular Filtration

Abstract

Marcello Malpighi (1628–1694) discovered the renal corpuscle and proposed that each glomerular body embraces the ampullar extremity of a tubule to form a “glandular follicle”. Thereafter, progress toward understanding the structure and function of the nephron stalled for two centuries, until William Bowman finally established the proper anatomic relationship between the glomerular arterioles, capillary tuft, and uriniferous tubule in 1842. In that same year, Carl Ludwig, in his Habilitations thesis, addressed the driving force that separates the watery and crystalloid constituents of the plasma from its “proteid” constituents. He dismissed both the “nonexistent” vital force and chemical theories for converting blood to urine, and deduced from geometric considerations that local hydraulic forces drive filtration of blood plasma through porous glomerular capillary walls. Ludwig’s theory was not universally accepted at the time and other influential figures, such as Heidenhain, continued to advocate the secretory formation of urine. Ludwig also had the foresight to envision that the hyperproteinemia resulting from glomerular filtration causes concentration of the urine by endosmosis into the peritubular capillaries. Several decades later, vant Hoff and others began to describe osmosis in terms of pressure using thermodynamic principles, which inspired Ernest Henry Starling to contemplate a role for the osmotic pressure of the plasma colloids in glomerular filtration. Starling wondered whether the minimum blood pressure below which formation of urine ceases might equal the osmotic pressure of the plasma colloids that oppose filtration. In 1897, he tested this hypothesis using a colloid osmometer of his own design with which he estimated the osmotic pressure of the blood plasma protein to be 25–30 mmHg or about 0.4 mmHg-gram −1 /liter −1 . Then he observed that raising the ureteral pressure to within 30–45 mmHg of the arterial blood pressure would stop the flow of urine in a dog undergoing diuresis. Thus, the hydraulic pressure across the glomerular epithelium must exceed the plasma colloid osmotic pressure by some small amount in order for urine to form. On this basis, Ludwig’s filtration hypothesis was deemed credible. Further evidence for glomerular filtration was published in 1924 by Wearn and Richards, who directly visualized the passage of indigo carmine into Bowman’s space from the blood in the course of performing the first-ever micropuncture experiments. Wearn and Richards interpreted their own findings as “indirect evidence that the process in the glomerulus is physical”.