Water Filtration and Reabsorption

Water Sources and Filtration

There are two main sources of water (H₂O) in the body:

• Ingestion of external food/drink (the majority)
• Endogenous water created as a product of aerobic respiration (negligible amounts)

In the glomerulus, water is filtered with other small solutes (e.g. Na⁺, K⁺ and glucose). Whilst the kidneys filter an average of 180L of water daily, only 1.5-2L of this is excreted in urine. This means almost 99% of filtered water is either reabsorbed into the circulation or enters the interstitium.

Reabsorption from the Nephron

Water reabsorption mainly occurs in three locations with high or regulated water permeability: the proximal convoluted tubule (PCT), the descending limb of the Loop of Henle and the collecting duct (CD).

Luminal water is reabsorbed into the intracellular or intercellular space, then into the interstitial space and finally into the peritubular capillaries or vasa recta (blood vessels running alongside the nephron). Water reabsorption occurs via 2 pathways:

• Transcellular movement – water moves into the tubule cell then into the interstitial space, requiring aquaporin channels (whether fixed or regulated) in cell membranes to confer water permeability
• Paracellular movement – water moves between tubule cells into the intercellular and interstitial space, which is prevented by the presence of tight junctions (without water pores) between cells

In most of the nephron, water reabsorption is heavily driven by osmotic gradients, largely generated by the transport of solutes. Since Na⁺ is the most abundant solute, water tends to follow the direction that sodium moves in.

CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

Fig 1
Water filtration and absorption in the nephron.

Proximal Convoluted Tubule (PCT)

Approximately 65–70% of filtered water is reabsorbed from the PCT into peritubular capillaries. It is facilitated by the permanent presence of aquaporin-1 (AQP-1) channels, conferring high water permeability for transcellular reabsorption, allowing water to passively follow osmotic gradients across cell membranes. Around 20% of reabsorption is paracellular.

Filtered sodium is actively reabsorbed from the tubular lumen via sodium glucose linked transporters (SGLTs). This Na⁺ reabsorption increases the tubular intracellular fluid concentration compared to the filtrate, creating an osmotic gradient for the transcellular and paracellular reabsorption of water. Thus, water is passively reabsorbed from the lumen into the cell and interstitial space.

Water reabsorption in the PCT is iso-osmotic, meaning that by the end of the PCT, the concentration of water in the filtrate and interstitial space (plasma) is almost the same.

Thin Descending Limb of the Loop of Henle

Approximately 20% of filtered water is reabsorbed in the Loop of Henle, primarily in the thin descending limb. It is highly permeable to water due to the presence of AQP-1 (meaning H₂O molecules are able to move freely across its membranes) whilst being impermeable to solutes. Water reabsorption occurs via transcellular and paracellular movement into the vasa recta.

An osmotic gradient exists between the isotonic filtrate entering the lumen and the hyperosmotic medullary interstitium. This gradient is generated by the countercurrent multiplier mechanism, driven by the active transport of Na⁺, Cl^– and K⁺ from the tubule into the medulla, via NKCC cotransporters in the thick ascending limb.

Since the ascending limb is impermeable to water, solute can be reabsorbed without water, increasing the osmolarity of the renal medullary interstitium. The osmotic gradient created is essential for enabling water reabsorption in both the descending limb and the collecting duct.

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

Fig 2
Diagram showing osmotic gradients set up by the thick ascending limb allowing reabsorption of water from the thin descending limb in the loop of Henle

Collecting Duct

In the collecting duct, H₂O reabsorption is regulated by antidiuretic hormone (ADH). ADH is produced in the hypothalamus and secreted by the posterior pituitary gland in response to decreased plasma volume or increased plasma osmolality. Tight junctions do not allow passive paracellular water reabsorption making regulation more effective.

ADH acts on principal cells in the collecting duct by binding to V2 receptors. This triggers an intracellular cAMP-mediated signalling pathway resulting in insertion of aquaporin-2 (AQP-2) channels into the apical surface of the principal cell, increasing permeability to water.

Water can then move down its osmotic gradient from the tubular lumen into the principal cell, hyperosmotic medullary interstitium (created by the loop of Henle), and finally into the peritubular capillaries and vasa recta.

In the absence of ADH, the collecting duct remains relatively impermeable to water, resulting in dilute urine. In the presence of ADH, increased water reabsorption leads to concentrated urine.

Reabsorption into the Circulation

Water that enters the interstitial space is reabsorbed into the peritubular capillaries (PCT and collecting duct) or vasa recta (loop of Henle and collecting duct) which run alongside the nephron.

The reduction in pressure across the glomerulus and the retention of plasma proteins during glomerular filtration means blood within the capillaries and vasa recta has a relatively high oncotic and low hydrostatic pressure. This creates a strong driving force for the reabsorption of water from the interstitium into the bloodstream via osmosis.

The vasa recta is also responsible for maintaining the medullary osmotic gradient through a countercurrent exchange mechanism.