Fluid/solute handling by the PCTOsmotic diuresis



Overview

Osmotic diuresis is excess loss of water due to the filtrate in the proximal convoluted tubule being hypertonic and interfering with the usual process by which this segment of the nephron reabsorbs most of the fluid and solutes in the kidney. Hyperglycaemia (diabetes) or mannitol (administered as an osmotic diuretic) can cause this simple effect, and there little that the remaining segments of the nephron - or homeostatic fluid/solute mechanisms - can do to compensate for the loss of water and solutes.


Fluid and solute handling by the proximal convoluted tubule (PCT)

Recall that most tubular reabsorption happens in the PCT: two thirds of total solutes and water together (hence it is isosmotic reabsorption), including all glucose under normal conditions. Figure 1 is a simplified overview of the basic mechanism of PCT reabsorption. Some key points are:

  • The primary mechanism driving reabsorption is the Na+/K+-ATPase establishing an electrochemical gradient across the tubule wall. Without this, little absorption would occur.
  • There is only a small an osmotic gradient along the length of the PCT between the filtrate and the interstitium, and it is due mainly to simply the (slightly) increasingly hypotonic nature of the filtrate as solutes are absorbed along its length.
  • The PCT is very permeable to water flowing in either direction.
  • Most (65%) of the water and solutes are reabsorbed via the paracellular route in the PCT.
  • In short, the PCT reabsorbs fluid and water using weak forces that are usually present. A metabolic poison (disrupting the Na+/K+-ATPase) or an alteration in filtrate osmolality will compromise this simple system.

osmotic diuresis

Figure 1: 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”.


Osmotic diuresis

The fluid and solute reabsorbing power of the PCT can be undone by simply making the filtrate hypertonic. There are two common situations in which this might occur:

  • Hyperglycaemia: when blood sugar is elevated, filtered glucose saturates the Na+/glucose transporter and remains in the filtrate within the PCT. This makes the filtrate hypertonic.
  • Mannitol infusions are sometimes given as a diuretic to eliminate water from the body (to relieve elevated intracranial pressure, in particular). Mannitol is excreted by the kidney, but is not reabsorbed at all, so remains in the filtrate, making it hypertonic.
Reabsorption in the PCT is quite efficient when the filtrate has normal osmolality, but if the filtrate becomes significantly hypertonic, water will travel in the opposite direction towards the tubule, again taking some solvents via solvent drag. The electrochemical gradient established by the Na+/K+-ATPase cannot overcome the brute physicochemical force of osmosis pulling water and solutes into the tubule lumen via the highly water-permeable paracellular pathway. Homeostatic mechanisms that might counter osmotic diuresis in the PCT are powerless because they do not alter the permeability of the paracellular route of water and solute egress. Because so much fluid and so many solutes are usually reabsorbed in the PCT, the rest of the nephron has little capacity to compensate. Furthermore, in hyperglycaemia the PCT is the sole site of glucose reabsorption, so the continual presence of excess glucose - and its osmotic effect - in the filtrate will compromise downstream mechanisms in the nephron. The result is usually polyuria leading to dehydration if not managed in a timely and appropriate manner. In hyperglycaemia, insulin administration will lower blood glucose, restoring plasma and filtrate osmolality to normal and thereby halting fluid loss.




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