The glomerulusProximal convoluted tubuleLoop of HenleDistal convoluted tubuleCollect duct



Overview

The nephron is both a wonderfully complex piece of physiology, and the bane of students of physiology. It takes baby-steps to get from a simple overview of the basic functions of the various parts down to the molecular mechanisms responsible for driving the movements of different solutes in blood and urine. Let’s start with the simple overview:

nephron overview


The glomerulus

The glomerulus is a network of capillaries located within the Bowman’s capsule. It is supplied with blood by afferent arterioles, which arise from intrarenal arteries. Blood leaving the glomerulus does not enter veins, but is carried by the efferent arterioles to the peritubular capillaries surrounding the rest of the nephron and thence to renal veins.

The endothelial cells of the glomerulus are porous, containing many small fenestrations which allow the passage of just about everything but the cellular contents of blood. However, only specific molecules manage to traverse the thick basement membrane between the glomerular endothelial cells and the epithelial cells of the capsule. Small ions and molecules such as Na+ and glucose are filtered, while large proteins in blood such as albumin are retained in the capillaries. The rest of the nephron is dedicated to getting taking back these ions and molecules – and water - as required


The proximal convoluted tubule (PCT)

About 65% of total reabsorbed solutes and water are reabsorbed along the length of the PCT, including all glucose. The primary mechanism driving reabsorption is the Na+/K+-ATPase establishing an electrochemical gradient across the tubule wall. Without this, little absorption would occur. Most (about 65%) of the reabsorbed solutes follow the paracellular pathway by “solvent drag” – dragged by the movement of water through this pathway. Some drugs reabsorbed in this way are actively secreted by a variety of pumps present within the PCT epithelial cells. Ammonia is also secreted in the PCT.
proximal tubule

Simplified overview of reabsorption by the proximal convoluted tubule. Multiple transport systems have been combined for clarity. Reabsorption is driven by the action of the Na+/K+-ATPase which drives Na+ out of tubular epithelial cells. This provides the electrochemical drive for the Na+/H+ exchanger, as well as a variety of other Na+ co-transport mechanisms (.e.g. Glucose, amino acids, bicarbonate, phosphate etc.). Water then follows these solutes via the paracellular route, taking with it a considerable proportion of reabsorbed electrolytes (ca. 65%) via “solvent drag”. Angiotensin II directly increases the activity of the Na+/H+ exchanger, increasing Na+ reabsorption.

The loop of Henle

The loop of Henle is the hardest part of the nephron to understand and deserves its own separate entry. The function of the loop of Henle is to maintain the hyperosmotic nature of the renal medulla, which acts as a sponge to attract water out of the collecting ducts. In the process, about 25% of Na++, Cl- and water are also reabsorbed in this region of the nephron. The key to the functioning of the loop of Henle is the active transport process in the ascending limb (see below) which drives Na+ and other ions out of the filtrate and into the interstitium. This limb of the loop of Henle is impermeable to water, so the result is a dilute filtrate. Furosemide (AKA frusemide) –and similar “loop diuretics” – block the Na+/K+/Cl- cotransporter which is essential to this process, inhibiting the ability of the kidney to concentrate urine and so causing diuresis.

loop of henle


Distal convoluted tubule (DCT) and cortical collecting duct

There are slight variations along the length of the DCT as it becomes the collecting duct, but we can construct a simple model to summarise overall function in this segment. Sodium is cotransported with chloride by the Na+/Cl- symporter into DCT cells and is pumped out the basolateral side once again by the Na+/K+-ATPase pump. One of the Na+-retaining actions of aldosterone is to upregulate the expression of the Na+/K+-ATPase pump to drive more Na+ out of the filtrate. The Na+/Cl- symporter is sensitive to the thiazide class of diuretics, which act in this segment to inhibit NaCl (and hence water) reabsorption. About 6% of filtered Na+ is reabsorbed in the early part of the DCT and about 2% in the later regions and in the cortical collecting duct. The DCT is also the primary site of Ca2+ reabsorption, which occurs via apical entry through calcium channels and removal from the cell by the Ca2+/H+ exchanger. Finally, regulation of acid base status occurs in the DCT via secretion of protons and reabsorption of HCO3- (detailed here).

distal tubule



Collecting duct

By the time filtrate reaches the collecting duct, it has an osmolality of around 300 mOsmol/kg and is composed mostly of urea. The permeability of the collecting duct is controlled by antidiuretic hormone (ADH, AKA vasopressin). In the absence of ADH the collecting ducts express few water channel proteins (aquaporins), which allow free movement of water. Under these conditions, the hyperosmolality of the renal medulla is unable to draw water out of the collecting ducts and dilute urine is produced. When ADH release is triggered (by osmoreceptors in the brain), aqueoporin expression is increased and water flows freely into the medulla where it is picked up by peritubular capillaries. This concentrates urine, restricting water loss by the body. This is the final site for Na+ reabsorption (about 1% of filtered Na+ is reabsorbed here), which occurs via apical entry through Na+ channels (Epithelial Na+ channels, ENaC) and exit from the cell via the Na+/K+-ATPase pump . The diuretic amiloride blocks ENaC, inhibiting this process, whereas aldosterone upregulates ENaC expression.

collecting duct




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