Filtration

The excretion of substances in urine is dependent on three processes: filtration, reabsorption and secretion. Urine formation begins with filtration of large amounts of fluid through the glomerular capillaries into the Bowman’s space. Blood enters the network of glomerular capillaries via an afferent capillary, and leaves through an efferent arteriole, rather than a venule. Vasoconstriction of the afferent arteriole creates high hydrostatic pressure inside the glomerular capillaries to force the movement of water and solutes across the capillary wall. The glomerular capillary membrane is comprised of three layers (instead of the usual two): capillary endothelial cells form a layer with 70 nm pores or fenestrae; a basement membrane of negatively charged collagen and glycoproteins; then the epithelial visceral layer of the Bowman’s capsule, known as podocytes, having long, foot-like projections that interdigitate to give filtration slits (slit pores, 25–65 nm). This glomerular filter, with each of the three layers having a negative charge, limits the filtration of a substance on both its molecular charge and size. The ultrafiltrate therefore consists of water, electrolytes, small molecules (<70 kDa) such as glucose, urea and amino acids, and is virtually protein-free.

Starling forces (Chapter 31) determine the movement of fluid between plasma and interstitium (tubule), summarised in Figure 37.2. Renal blood flow and glomerular filtration rate (GFR) are maintained at a relatively constant level, a process known as autoregulation. This involves two feedback mechanisms: an intrinsic myogenic property of blood vessels to resist stretching during increased arterial pressures; and the tubuloglomerular feedback involving the macula densa, a short segment of tubular cells (at the end of the ascending limb of the loop of Henle), which together with vascular granular cells (medial layer of the afferent arteriole adjacent to the vascular poles of the glomerulus) form the juxtaglomerular apparatus. The macula densa cells sense changes in tubular fluid NaCl concentration and volume/flow rate in volume delivery in the distal tubule, secreting vasoactive substances that control the vascular tone of blood vessels (such as adenosine, prostaglandins) and the control of renin release from the granular cells (see Chapter 39).

GFR can provide an estimate of the efficiency of renal filtration and hence renal function. In clinical medicine, creatinine (a metabolite of skeletal muscle creatine phosphate breakdown) is used to estimate GFR as it is almost completely cleared from the body by glomerular filtration.

The ultrafiltrate passes along the nephron tubule where its volume and content are altered by the processes of reabsorption (movement of filtered substance from tubular lumen to tubular capillaries) and secretion (movement of substances from vascular compartment to tubular fluid).