The Carnal Carnival: PEE!

Apr 15 2011 Published by under [Medicine&Pharma]


Click image for original source

This month, the Carnal Carnival feature pee! May I present a collection of recent blogs about kidneys and the golden fluid they produce.

First up, Uremic Frost presents an obituary for Edith Helm, the first female kidney transplant recipient. A 20-year-old newly-wed when she found out she had months to live, she underwent the transplant and ultimately became the first transplant recipient to give birth. She died at 76 in her home state of Oklahoma.

Next, we had an unusual event this week, documented by the Renal Fellows Network. The event was presentation of a new predictive equation for patients who have lost at least 40% of normal kidney function, and it predicts the two year risk of end-stage kidney failure with at least 90% accuracy. As the equation was presented at the World Congress of Nephrology, it also got published in JAMA and an app including the equation was released for all major mobile platforms. Very Media 2.0.

University of the Kidney presents a cool video on the dream of organ regeneration. Over at Nephron Power an excellent slide show on cystic kidney diseases can be viewed.

Precious Bodily Fluids considers how fast your creatinine level would rise if someone really removed both kidneys and left you in a bathtub of ice.

Finally, I have to give my Scientific American guest blog another shot-out. Who wouldn't want to reminisce about Paradoxical Polyuria? Ah...good times.

So enjoy learning a bit more about the golden fluid, and try not to pee your pants in the liquor store!

- Posted using BlogPress from my iPad

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April Carnal Carnival: The Golden Fluid

Mar 16 2011 Published by under Wackaloonacy

A pissing good time...

WhizBANG! has the immense pleasure of hosting The Carnal Carnival on Friday, April 15. The theme will be urine and urination.

Humans, animals, statues... Anything goes as long as that golden fluid (or lack thereof) is involved.

So start sending links to goldenurine@gmail.com or you may regret it. This carnival will be epic!

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What I Am Reading: Chimera Version

Mar 15 2011 Published by under [Medicine&Pharma], [Science in Society]

Click to Pre-order at Amazon

One of the joys of my blogging life is getting to read books before they are officially published. This year, the Science Online swag bag included Blood Work: A Tale of Medicine and Murder in the Scientific Revolution, a book that kept me occupied for a few days. Science? Check. Medicine? Check. Murder mystery? Check.

Holly Tucker, a faculty member of Vanderbilt University,  weaves a number of historical and political intrigues into a story of medical experimentation that results in murder.

The saga proceeds in the 1600s. French and British physicians and scientists race to learn new facts about anatomy and physiology. Great rewards awaited the first to publish (gee, does that sound familiar?), and governments (royalty) began to fund academies to help assure the place of their investigators in the race for knowledge. Within France, where the murder in question occurs, political clashes between a private academy begun by Henri-Louis de Montmor and that funded through the crown, as well as the Parisian medical establishment versus other schools within the country, complicate the interpretation and dissemination of experimental data (once again, sound familiar?).

The primary character, Jean-Baptiste Denis, longs to make his mark in Parisian society, despite being an upstart of lesser birth trained outside of the Parisian school. He becomes convinced that transfusion will provide transport for his social goals, and begins experiments with dog-to-dog blood transfers. These procedures are described in excruciating detail -  after all, there was no anesthesia, so dogs were muzzled and tied to tables for the procedure. Anticoagulation was unknown, so blood had to be transferred directly from one dog to the other without storage, and the transfer took place through small metal stems and quills. The donor dog underwent cut-down to access an artery, and that dog's blood pressure drove the blood into the recipient's vein, also accessed via a cut-down. Going from a large dog to a small one seemed to work better, and the small dog often seemed "livelier" after the procedure. The donor dog? Not so much.

He then wanted to proceed to animal-to-human transfusion. This proposition scared folks, not because of the issue of transfusion reactions not yet described; no, people were terrified that they could become physical chimeras. Receive the blood of a calf, and you might wake up with the face of a cow. The artwork in the book shows these amazing chimera images!

Click for Source

Denis eventually found "volunteers" for his experiments, the first a desperately ill 16-year-old boy who the barber-surgeons had bled more than 20 times. For his donor, he chose a sheep. What could be more helpful than the blood of the lamb, the symbol of Jesus' sacrifice? The boy felt better the next day, apparently cured of his two month fevers. Denis then persuaded a butcher, perhaps the one who provided the lamb, to undergo the procedure. He also did well and took the lamb home for supper.

Denis immediately reported his success, and then decided to go for the big-time. Antoine Mauroy, once a valet, now roamed the streets of Paris raving, an infamous mad man. Denis planned to transfuse the blood of a calf into Mauroy to attempt to heal his illness. The transfusion reportedly quiets his troubled soul, and he returns to his wife, Perrine, a calmer, saner husband. After a few weeks, she returns to Denis requesting another treatment because Mauroy's ravings have returned. Denis obliges, and a few weeks later, Antoine is dead.

I love mysteries, and I love biomedical science, so the book resonated with me. My favorite parts were some of the anecdotes illustrating various points, especially those that involved kidney disorders. I am, after all, a nephrologist.

Animals and their parts were common folk remedies of the time. Below follows a cure for kidney stones:

In the month of May distill Cow-dung, then take two live Hares, and strangle them in their blood, then take the one of them, and put it into an earthen vessel of a pot, and cover it well with mortar made of horse dung and hay, and bake it in an oven with household bread and let it still in an oven two or three days, until the hare be baked or dried to powder; then beat it well and keep it for your use. The other Hare you must flew, and then take out the guts only; then distill all the rest, and keep this water; then take at the new and full of the moon, or any other time, three mornings together as much of this powder as will lie on six pence, with two spoonfuls of each water; and it will break any stone in the kidneys.

Now that makes remembering to take a once-a-day pill seem easy.

I also loved learning that urine can be used as invisible ink!

Blood Work provides an interesting trip into the history of medicine and its scientific roots. The book becomes available on March 21.

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Vesicoureteral Reflux: What We Don't Know

Mar 01 2011 Published by under [Medicine&Pharma]

I received inspiration today for a post on the management of a common pediatric nephrology problem, vesicoureteral reflux (VUR for short).

I reviewed a meta-analysis over at my other blog since this is a serious medical topic fitting for my serious medical site.

For 50 years (my entire life) treatment has been recommended for this condition based on opinion and bad science. Now, we are finally sorting out what we should do based on evidence rather than what we thing we should do.

I can't believe it took this long!

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Growing Kidneys

Feb 16 2011 Published by under Nephrogenesis

H/T to @sciliz for the topic suggestion.

Normal Kidney Development

Pronephros and Mesonephros (Click for Source)

The first structure to develop in any vertebrate embryo, the pronephros, consists of a single filtering unit and tubule. In some species these structures do not attach to each other; a funnel-shaped structure with finger-like projections "waves" fluid from the site of filtration into the tubule. In some species the pronephros becomes the adult kidney, but in humans and "higher" vertebrates, the pronephros exists only briefly. It induces development of another structure, the mesonephros.

This mesonephros forms multiple filtration units and tubules capable of urinary function, albeit briefly in humans. These ducts become incorporated into the genitourinary system as a more complex metanephric kidney forms. In some animals, such as the zebrafish, the mesonephric kidney is the adult kidney.

Why Zebrafish?

Since the zebrafish kidney finishes at the mesonephric stage, it cannot be a perfect model for studying human kidneys; however, it offers many advantages over other models.

For example, the zebrafish embryo is transparent, making it easy to look at things without killing or cutting up the fry:

Zebrafish Embryonic Development (Link to YouTube Video)

Zebrafish breed rapidly and continuously with a generation time of 3 months.

Sequencing of the zebrafish genome facilitates creation of fish labelled with a variety of fluorescent markers, so specific structures can be studied in situ in live critters. Zhou et al labelled glomerular cells with a red marker and tubular structures with green fluorescent protein to make photos of normal nephrogenesis:

Mesonephrogenesis in cdh17::GFP/pod::mCherry double-transgenic zebrafish. A: schematic graph illustrating the transgene structures of pod::mCherry and cdh17::GFP. Tol2-L and Tol2-R are Tol2 transposon elements to facillite the transgenesis. B: lateral view of a 9 days postfertilization (dpf) larva. Podocytes in pronephric glomeruli (arrow) are marked with mCherry fluorescence (red) and pronephric tubules and ducts are labeled with GFP fluorescence (green). cdh17::GFP expression is also present in the intestinal epithelia, where the endogenous cdh17 is expressed (12). C: lateral view of a 14 dpf larva that developed the first pair of mesonephric glomeruli (arrowheads) with matured podocytes-expressing mCherry (red). D: ventral view of a 28 dpf juvenile. Multiple glomeruli (red) are visible at the anterior and medial portions of the mesonephric kidney with convoluted mesonephric tubules. E: ventral view of a 36 dpf juvenile. More mesonephric glomeruli and more convolutions of tubules developed in the anterior and medial regions. A few nephrons are present in between the rostral and medial regions as well as in the posterior region. F: ventral view of the whole mesonephric kidney in a 6-mo-old adult. ANDR, anterior nephron-dense region; MNSR, medial nephron-sparse region; MNDR, medial nephron-dense region; PNSR, posterior nephron-sparse region. Note symmetric groups of nephrons (arrowheads) in PNSR are segmentally distributed. Anterior to the left in all the panels.

Some background nephrogenesis can occur throughout the life of the zebrafish, but it slows down after 6 months of age. They then created a fish with the green marker linked to the zebrafish homolog of Wilm's Tumor 1, a marker of renal progenitor cells. Once again, podocin, a marker of mature glomeruli, drove the red marker. They then treated the fish with gentamicin, a nephrotoxic antibiotic, and showed that after kidney damage the zebrafish grew new nephrons:

Gentamicin-induced renal injury triggers de novo regeneration of mesonephric nephrons. A, A': injection of PBS does not increase mesonephrogenesis at 5 days postinjection (dpi). The green puncta are wt1b::GFP-expressing cells at the neck of matured nephrons. B, B': by 5 dpi of gentamicin, there is an increased number of developing nephrons. C, C': at 9 dpi of gentamicin, wt1b::GFP expression indicates the progression of these newly made nephrons. D, D': level of nephrogenesis is still elevated at 14 dpi of gentamicin. E: quantification of wt1b-GFP+ nephron numbers postgentamicin-induced renal injury. *P < 0.05, **P < 0.01.

So zebrafish can grow new nephrons with genetic markers similar to those of humans in response to kidney damage. Why can't people? And can we learn how zebrafish achieve this feat and make it happen with human cells? Can these nephrogenic cells be used to grow new nephrons in different zebrafish?Using a similar fluorescent tagging technique,  Diep et al transplanted progenitor cells from a zebrafish bearing one label to other fish with different labels and demonstrated that these cells would form new kidneys in the recipient fish. These cells worked with progenitor cells in the recipient fish to form the new units:

a, Overview of the transplantation assay. b, A primary transplanted fish at 18 d.p.t. with cdh17:EGFP+ donor-derived nephrons (arrow; inset, higher magnification view; scale bar, 0.5 mm). c, Average number of donor-derived nephrons over time (error bar, one standard deviation; n, total fish per time point). d, Head kidney of a recipient at 34 d.p.t. showing expansion of renal tissue caused by cdh17:mCherry+ donor-derived nephrons (arrow; scale bar, 0.5 mm). e, A cdh17:mCherry+ donor-derived nephron showing functional uptake of 40 kDa FITC-conjugated dextran (scale bar, 30 μm). f, Connection of donor-derived nephrons (cdh17:mCherry+) with the cdh17:EGFP+ recipient’s renal system (scale bar, 10 μm). g, A mosaic nephron arising from the co-injection of a mixture of cdh17:EGFP- and cdh17:mCherry-labelled nephron progenitors. h, Overview of the serial transplantation assay. i–k, Donor-derived nephrons (cdh17:EGFP+, arrows) in primary-, secondary- and tertiary-engrafted recipients (scale bar, 0.5 mm).

The Take-Home Message

First, even if you do not love kidneys and urine as much as I do, you must admit that these studies employ cool technology and generate amazing photos. Both of these articles include supplementary photos and videos as well; you should click on over to the web sites and play!

More important, Diep et al show that progenitor cells can be transplanted. Some dormant cells may remain in metanephric kidneys (like we humans have) that we can eventually learn to stimulate to regeneration. Someday we may be able to produce progenitor cells in vitro using stem cells, and then inject them into failing kidneys.

Finally, even with their differences, zebrafish can teach us important things about the development of organs, as well as being cute and hardy pets for our tanks.

Articles:

Zhou et al: Characterization of mesonephric development and regeneration using transgenic zebrafish. Am J Physiol Renal Physiol 299:F1040-F1047, 2010.  doi:10.1152/ajprenal.00394.2010

Diep et al: Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. Nature 470:95-101, 2011.  doi:10.1038/nature09669

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My Pain Is Your Pain

Feb 03 2011 Published by under Acid-Base Disorders

So yesterday I went home with a headache, photophobia (light sensitivity), and chills. No VapoRub or Windex, but I feel better today; however, my drive to blog has been suppressed. Since I have to present to first year medical students tomorrow, this post will cover the same topic: the use of the anion gap in metabolic acidosis.

The body tightly regulates acid-base balance with short and long-term adjustment processes. The bicarbonate buffering system, which consists of CO2, water, and H+, provides the most important source of regulation.

Yup, the kidney gets rid of water. (Click for source)

Bicarbonate is generated by the kidney, H+ and water are excreted by the kidney, and CO2 can be excreted by the lungs. This equilibrium can be thought of as the balance between renal (kidney) and pulmonary (lung) processes.

Normal metabolic processes generate approximately 1 mEq/kg body weight per day of H+ that must be eliminated from the body or buffered and neutralized. Ingestion or generation of excess H+ or abnormal losses of bicarbonate may result in acid buildup. This process is called a metabolic acidosis. It can be easily diagnosed on a blood gas. In a patient with no pulmonary history, it may be suspected when the total CO2 (a measure of bicarbonate) on the electrolyte panel is low.

Blood is an electroneutral fluid. As part of the extracellular space, the primary cation in the serum is sodium. It must be balance by anions including chloride, bicarbonate, and a number of unmeasured substances. In normal states, plasma proteins constitute the bulk of the unmeasured anions. The anion gap is a measure of these unmeasured anions and can be calculated by subtracting the measured anions from the measured cation [Na – (Cl + Bicarbonate)] = Anion Gap. The anion gap is normally 12±4.

It is useful to classify metabolic acidosis by the anion gap. If the gap is increased, there are “new” unmeasured anions in the blood, either from the ingestion or production of an acid that has dissociated into H+ and its anion. Because the acid is electroneutral, the chloride remains normal.

If the kidney is unable to excrete H+, then bicarbonate is consumed and levels drop. Similar biochemical events result if bicarbonate is wasted, either from the gastrointestinal tract or via the kidney. In either of these cases, there is no “new” anion in the blood to electrically balance Na+, so chloride increases. This keeps the anion gap in the normal range.

I have demonstrated these types of acidosis in the video below:

High gap acidosis occurs with ingestion of drugs or toxins, or dysregulation of metabolism such as diabetic ketoacidosis or organic acidemia. Normal gap acidosis occurs with diarrhea, other forms of intestinal bicarbonate losses, and renal tubular acidosis.

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Embryology and Bird Droppings

Dec 01 2010 Published by under [Biology&Environment]

Last week I posted my usual Thanksgiving message to be glad you can pee. I made a cute drawing of a turkey to go with my sincere wishes.

Click image for source, including a video you will never forget.

Dr. Isis responded by asking if turkeys can pee. So today's post addresses bird urine and a bit of embryology.

Normal Human Urogenital Development

Studying human embryology makes one wonder how any of us come out normal. So many things can go wrong as all of these cells divide and migrate and die.

Initially the urinary tract, genital tract, and gastrointestinal tract all empty into a common opening called the cloaca.

Click for a great site about embryology.

In the later part of development, cells must migrate to form "walls" between various structures in humans, giving us the 2 or 3 openings expected. Sometimes this process goes wrong, and babies may be born with a persistent cloaca.

Bird Urogenital Systems

Birds skip this division of openings; their urinary, genital, and gastrointestinal tracts open into a cloaca that then exits the body. Birds also maintain internal gonads; in the absence of sex differences in plumage, it can be very difficult to tell a boy bird from a girl bird, short of surgery to examine the internal glands. Birds thus empty both urine and feces into this common pouch which exits the body via a single opening or vent (which is also used for sex).

Anatomy of Bird Droppings

Normal Droppings; click for original source.

When birds empty the cloaca, they both poop and pee. The dark portion of the dropping is fecal material which reflects the bird's diet. Clear urine evaporates quickly; bird owners may collect droppings on blotting paper to evaluate the volume of urine, as shown in the figure. The white material in droppings is composed of urates. Birds and some reptiles excrete these crystals in the feces rather than in urine via a process that allows maximal water conservation.

The Answer Is...

Our feathered friends do have kidneys and make urine. We just may not perceive it because they always do #1 and #2 simultaneously and the poop lasts longer than the pee.

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How Much Do You Love Urine?

Aug 14 2010 Published by under Wackaloonacy, [Etc]

What else would I show here?

First, a big thanks to everyone who has clicked by my new online crib since August 2. I am enjoying the traffic, and I am glad to see actual interaction happening on some posts.

Today is Saturday, a day when most of my loyal readers will be enjoying or despising the weather and a day off of work. What could make that better than the debut of...

wait for it....

you know it's coming....

I can feel the suspense....

drumroll, please....

THE WHIZBANG! SWAG SHOP!!!!!!

Yes, you can now show your love of this blog, the Scientopia site, and that golden fluid by plunking down a few bucks for stuff.

Of course, the standard tee comes in yellow.

Instant Classic

And we feature the full range of "hydration vehicles" for your pleasure - coffee cups, water bottles, and a beer stein.

Finally, the shop also offers more intimate garments to protect those bits that let your urine flow.

The WhizBANG! Thong

A small mark-up is included in the prices. Don't worry- I'm not planning to get rich on the blog!  These "profits" will be used to support groups that fund kidney research. After all, I am a Scientopian- collaborative, cooperative, and definitely not-for-profit.

So start shopping - you know you want those boxers!

Toilet image courtesy of PhotoXpress.

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