Aquaporins of the Kidney and Water Homeostasis - Anatomy & Physiology

()Map KIDNEY ELECTROLYTE BALANCE (Map)

The Importance of Maintaining Adequate Levels of Water

Too Little Water

• Inadequate perfusion due to low blood volume
• A build up of waste products due to insufficent urine volume
• Increased solute concentrations affect cell function
• Inability to sweat and control body temperature
• Death

Too Much Water

• Oedema
• Increased blood volume and therefore pressure could damage the CVS
• A decrease in solute concentrations disrupt normal cell function

The Ability of the Kidney To Alter the Water Content of the Body

• Take a dog which weighs 20kg and is drinking normally. It will produce 0.5l of water per 24 hours.
• If the dog drinks excessively it can produce 8ml urine/min to compensate meaning a total of 11 litres per 24 hours
• If a dog is denied water the production drops to a tiny 0.15 litres per 24 hours

The reabsorption of water can occur paracellulary - the main method in the proximal tubule or transcellulary - the main method in the distal tubule and collecting duct.

• Contrary to popular belief diffusion of water accross lipid bilayers (transcellulary) is too slow for most physiological processes
• Aquaporins solve this problem

• The reabsorption in the proximal tubule and loop of henle occurs as water follows the reabsorbed sodium via osmosis.
• The protein osmotic pressure coupled with the hydrostatic pressure of the peritubular capillaries effects the volume of water excreted or conserved also.

What are Aquaporins

• Family of membrane channel proteins
• Over a dozen homologous water transporting proteins make up this family in mammals
• Allow rapid transport of substances accross membranes
• Found in all life forms
• Commonly abbreviated to AQP
• Ones found in the kidneys are:
  • AQP1 - Tubules
  • AQP2 - Collecting duct
  • AQP3 - Collecting duct
  • AQP4 - Collecting duct
  • AQP6 - Collecting duct (intercalated cells)
  • AQP7 - Proximal tubule
  • AQP11 - Kidney
• They are colour coded according to their function
  • Water channels
  • Glycerol channels
  • Intracellular chloride channels
  • Function Unknown

• They allow the reabsorption of water, glycerol and chlorine from the filtrate
• Without them producing concentrated urine would be impossible

ADH and the Collecting Duct

The membrane of the Collecting Duct is practically impermeable to water. Therefore in order for water reabsorbtion from this part of the nephron to occur it is vital that aquaporins are inserted. This is the role of ADH. These channels are always present on the basolateral membrane of the epithelial cells but their presence and concentration on the apical membrane is reliant on the concentration of ADH in the blood. ADH works by binding to V₂ receptors on the basolateral membranes of the cells and activates adenyl cyclase creating cyclicAMP (cAMP) this in turn activates protein kinase A which causes protein phosphorylation. This causes vesicles with ready made glycoprotein AQP2 aquaporins in their membranes to move to the apical cell membrane and insert the aquaporins via exocytosis. This rapidly increases the water permeability and allowing reabsorption

Species Variation of the Ability to Conserve Water

Mammals and birds can produce urine both more and less concentrated than plasma in order to conserve or excrete water. The excretion is done without interefering with the levels of solute excretion. The ability to concentrate urine depends greatly on a species access to water. Animals with access to lots of water have less of a need and therefore have not evolved great mechanisms to concentrate urine for example the beaver. However animals who have limited access to water and say live in more arrid environments such as the kangaroo rat which lives in a desert habitat have evolved very good mechanisms to reabsorb lots of water and produce a very concentrated urine.

Nephron Species Differances

The variation in nephron structure is pivotal to the to the species differances with regard to the ability to concentrate urine. Broadly there are two structures.

Juxtamedullary Nephrons

These nephrons have glomeruli in the cortex and loops of henle which descend into the medulla. These are the commonly described nephrons. Significant urine concentration is achieved thanks to the hyperosmolar medulla achieved via the counter current multiplier drawing water out of the collecting ducts.

Cortical Nephrons

These nephrons have glomeruli in the outer cortex and their loops of henle barely penetrate the medulla. They have very limited concentrating ability.

The length of the loop of henle is the determining factor with regard to how concentrated urine an animal can produce. In species which produce very concentrated urine almost if not all of their nephrons are juxtamedullary in type and they tend to have very long loops of henle. However animals such as beavers where dehydration is not really an issue have very short loops of henle and excrete dilute urine. One surprise is however that the kangaroo rat which can concentrate urine to the equivalent of a 20% saline solution actually has shorter nephrons than some larger species with less ability to concentrate urine. This has been attributed to it having a much higher metabolic rate and thus more active transport meaning greater gradients can occur on any given length of its loop of henle.

The following table shows a comparison between the maximum concentrating abilities of the kidneys of various mammals. Data from Physiology of Domestic Animals - Sjaastad, Hove and Sand. For full text referance see the Reference Material section.

Species	Max Urine Osmolarity (mosmol/l)	Urine/Plasma Concentration Ratio
Beaver	520	2
Calf	500	2
Pig	1100	4
Humans	1200	4
Cow	1400	5
Sheep	3500	11
Horse	2000	7
Dog	2500	8
Cat	3000	10
Kangaroo Rat	5500	18