Tuesday, May 18, 2010

Beyond the kidney

Mostly I think about the bladder, in a professional sense, as a possible site for obstruction to be ruled out. Occasionally, when I’m personally reminded about it, I wonder how much urine it can hold. (Pearl from residency: never start a procedure on an empty stomach or with a full bladder) Recently, I had a chance to learn about the bladder while researching an article and discovered several fun facts:

- urine empties into the bladder every 10-15 seconds
- the bladder can hold comfortably between 350-550 cc (12-18 oz) of urine for several hours;
- the urge to urinate usually starts when it has anywhere between 150-300 cc or urine; it can be overridden voluntarily to volumes of 600-800 cc
- speaking of causes of bladder outlet obstruction, the largest bladder stone ever removed (per Guinness world records, 2007 edition) weighed 1.9 kg and measured 17.9 by 12.7 by 9.6 cm

The bladder is able to stretch to accommodate such swings in urine volume thanks to two properties of its epithelium. The first one is a folded apical membrane, which unfolds as the bladder is filling, changing the shape of the top layer of urothelial cells – also called umbrella cells -- from a rounded one to a more flat, squamous one. The second feature is a collection of membrane vesicles, tethered close to the apical surface by cytoskeletal fibrils. As the cell stretches and becomes flatter, the vesicles fuse with the apical membrane, increasing its surface.

The bladder is normally impermeable to the components of urine: molecules, such as urea, ammonia, and water, which usually freely travel through epithelial membranes. Aside from the presence of tight junctions between cells, this impermeability is a function of the composition of the lipid bilayer of the apical epithelial membrane, where the specific arrangement of lipid hydrocarbon tails impairs travel of these molecules across the bilayer. In addition, special proteins, called uroplakins, form aggregates called plaques. These plaques occupy 70-90% of the surface of each cell and help keep urea and water out. When uroplakin was knocked out in mice, their urothelium became permeable to urea, and, to a lesser extent, water.

Interestingly, the urothelium has amiloride-sensitive ENaC–type channels, present at very low levels in normal human bladders (and with different subunit stoichiometry in different mammals). Channel expression may increase in states of elevated bladder pressure, such as in bladder obstruction, an observation consistent with a recent report suggesting that the role of the ENaC -type channels appears to be more important in mechanosensation.

Some interesting reviews and relevant articles can be found here, here, here and here.

Posted by Marta Hristova, MD, PhD


Anonymous said...

Great post about uroplakins. Nathan posted one complementary to this back in November: http://renalfellow.blogspot.com/2009/11/uroplakins.html Please add labels (urinary tract infection, microbiology, urology) to this post so it can be referred to later on. Thanks.

Matt Sparks said...

Thanks for the comments