It’s important to find balance in life, and that’s true for nitrogen as well.

Incoming!

When your body breaks down proteins in the liver, it’s left with wastes containing nitrogen as a byproduct. Ammonia is the simplest form, but it is quite toxic, so it needs to go somewhere or get converted into something else as soon as possible.

If you’re a fish, you just let that ammonia dissolve into the water around you. If you’re a mammal, you convert it to urea, which uses up a little extra energy but isn’t as toxic as ammonia, and then the kidneys filter it out and it leaves the body in urine.

If you’re a bird or a reptile, you convert that ammonia to uric acid and excrete it directly as the pasty white urate portion of droppings. (It’s uric acid if there’s a free proton involved, or urate if something else like sodium is attached. For our purposes, consider urates and uric acid to be the same thing.) Creating uric acid uses up more energy than creating urea, but it means birds and reptiles don’t have to use as much water to get rid of their nitrogenous wastes.

But wait, there’s more!

Mammals also produce uric acid. You might have vague memories of A-T C-G DNA pairs from your biology class. Adenosine and guanine are purines. When those purines are broken down, uric acid is produced instead of urea.

But mammals don’t excrete urates, so where does it go? The answer is that uric acid is dissolved in the blood until the kidneys grab it and it goes out in the urine.

Except when it all goes wrong

What happens if the kidneys don’t filter out the uric acid? If the kidneys don’t do their thing, the uric acid builds up in the blood until it crystallizes in the joints. This painful condition is called gout. For people prone to getting gout, one way  to avoid it is to eat a diet low in purines. Decreasing the purines coming into the body leads to decreased uric acid production by the liver, which hopefully avoids an attack of gout. This is such a common problem that you can come up with a list of high-purine foods to avoid with one google search.

What happens if the blood carrying nutrients absorbed by the intestine goes around the liver instead of going through it? Normally everything goes through the liver first, so any ammonia can be converted to urea before it has a chance to cause problems. But sometimes the blood vessels don’t develop correctly or go wonky later in life, and then there’s a higher concentration of ammonia plus uric acid in the blood and urine, and those two compounds like to combine together in the bladder to form ammonium urate stones. Bladder stones are no fun.

(Anecdote time! There was a cute older Pomeranian at the practice I worked in before vet school. His chart had notes in large letters from when he was a neutered as a puppy warning that this dog took a really, really long time to recover from anesthesia. Then while I was in vet school, this dog came in to the practice have bladder stones removed on a day when I happened to be visiting. The stones turned out to be ammonium urate. And then when I was a senior student, this dog came to the vet school to have surgery to fix the blood vessel that was shunting blood around his liver. That was one of those “yep, it all adds up” moments, though that dog almost made it his entire life without having his liver shunt diagnosed or corrected.)

What happens if you’re a Dalmatian? Yes, I said it — being a Dalmatian is an adverse medical condition. Dalmatians metabolize their purines in an odd way, and as a result end up with higher uric acid in the blood. Plus they have some problem in their kidneys as well, and possibly yet another (unknown) issue and that all leads to Dalmatians being predisposed to forming ammonium urate bladder stones. One of the treatments for this is a drug that affects purine metabolism in the liver, so they produce more of a different byproduct (xanthine) and less uric acid. That cuts down on the ammonium urate stones in the bladder, but occasionally causes xanthine stones instead. Sometimes you just can’t win.

Want to know more?

https://www.diffen.com/difference/Purines_vs_Pyrimidines

https://opentextbc.ca/biology/chapter/22-4-nitrogenous-wastes/

Textbook of Veterinary Internal Medicine, Ettinger & Feldman, 5th edition. (A book made from paper. How quaint!)

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During Fun Facts Friday, I talk about something I think is interesting. Do you have questions? Suggestions for a future post? Add a comment below!

I once saw a rabbit with the presenting complaint of “face twitching”, and then I gave her a drug that could have easily killed her, but instead she was cured and went home with three babies. This is the biology behind her story.

Calcium, it’s what’s for dinner.

As a kid you were encouraged to drink milk so you would build strong bones, but the flip side is that you need bones with a lot of calcium to help regulate the amount in your blood. Bones are a bit like a lending library for calcium. Need some? Pull it from the bones. Have extra? Store it in the bones for a rainy day.

Calcium is used everywhere in the body. It’s necessary for smooth muscle contraction, it affects the length of time before cardiac muscle is ready to go again, and low calcium can cause neuromuscular irritation. Name any system in the body, and calcium will somehow be important there, too.

Rabbits Are Just Tiny Horses

In many ways rabbits really are more similar to horses than dogs or cats. Prone to dying from gut issues, check. Foot issues, check. And unlike most mammals other than horses, rabbits absorb most of the calcium in their diet, and then get rid of the extra in their urine.

As you can imagine, having sludgy urine with a bunch of calcium sediment in it is not comfortable, and can lead to bladder stones. Because of this, most rabbit owners feed their rabbits grass hay, which has about a third of the calcium found in alfalfa. Not as much calcium in the food leads to less sludgy urine. It’s a win for everyone.

Except…

There are times when a rabbit might need a little extra calcium. Pregnancy and lactation are the two biggest ones. In the case of my patient, the pregnancy was an “oopsy” according to the owners, though I would argue that if you have intact rabbits, they will find a way, as indeed these rabbits had. (Rabbits also get a lot of uterine cancer, so just spay your pet rabbits, okay?) The owners hadn’t planned on breeding the rabbits, and weren’t really prepared for it, and all their rabbits were eating grass hay.

Everything was going well until the rabbit reached the end of gestation and started producing milk in preparation for the babies that would soon be there. The calcium balance was already teetering on the edge because the fetuses were using calcium for their bones, and suddenly the calcium level in doe’s blood wasn’t high enough. That caused two immediate problems in this patient:

1. Because the uterus is made up of smooth muscle, and smooth muscle requires calcium to work, the rabbit stopped having contractions.
2. Low calcium caused neuromuscular excitation. In dogs you often see that as a stiff gait, but that’s a little harder to see in a rabbit. What we did see were spasms on one side of the rabbit’s face.

(It could have been worse. In birds with low calcium, often the first thing the owner notices is the bird having a full-blown seizure. That’s often fatal.)

Anyhow, we were pretty sure of the cause of this rabbit’s problems, so we knew the solution: give the rabbit calcium. That’s easy enough. If her symptoms had been less severe, we could have just corrected everything with diet changes, but those kits were ready to be born and couldn’t wait. So IV calcium was called for. Pump her full of calcium then pop her in a cage and wait for the babies, right?

Hold Up There

This is another one of those cases where drugs affect different muscle types in different ways. If there’s too much calcium in the blood, cardiac muscle takes longer to repolarize, which is a fancy way of saying the heart slows down. If you give calcium too quickly, you can literally stop the heart.

So as much as it would have been nice to give the rabbit a big dose of calcium and then let her relax in a quiet place to give birth, I had to stand there for fifteen minutes with a syringe in my hand, monitoring her heart rate. Naturally the minute her face stopped twitching, a kit popped out the back end.

(I had been hoping she wasn’t actively in labor yet because stressed rabbits can eat their young, and I’m not sure what is more stressful than an exam table in a vet hospital with a resident staring at you. Luckily this rabbit was used to people.)

In this case the doe and all her kits went home healthy, and that doesn’t happen all that often in avian and exotics practice.

Links

Want to know more? Try some of these resources:

• https://www.harcourt-brown.co.uk/articles/free-food-for-rabbits/calcium-and-rabbit-food
• http://www.pethealthnetwork.com/dog-health/dog-diseases-conditions-a-z/hypocalcemia-dogs
• https://www.ncbi.nlm.nih.gov/books/NBK279022/
• https://myemail.constantcontact.com/Don-t-give-IV-calcium-to-a-standing-cow.html?soid=1105909906452&aid=ipnV4kiUjwU
• https://med.libretexts.org/Bookshelves/Anatomy_and_Physiology/Book%3A_Anatomy_and_Physiology_(Boundless)/17%3A_Cardiovascular_System%3A_The_Heart/17.3%3A_Cardiac_Muscle_Tissue/17.3A%3A_Mechanism_and_Contraction_Events_of_Cardiac_Muscle_Fibers

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During Fun Facts Friday, I talk about something I think is interesting. Do you have questions? Suggestions for a future post? Add a comment below!

You probably already know that birds are just dinosaurs that survived the last apocalypse. They have a lot of big differences when compared to mammals (feathers! eggs! a cloaca!), but there are also differences that are less obvious, such as the ones in the eyes.

But First, A Refresher

High school science classes are big on memorizing things, so you’ve probably heard of the three types of muscle:

• Cardiac: In the heart, not under voluntary control. (If cardiac muscle were under voluntary control, most people wouldn’t survive their first breakup.)
• Smooth: Around blood vessels and organs, also not under voluntary control. (If it were under voluntary control, pharmaceutical companies wouldn’t be making so much money on little blue pills.)
• Skeletal: These are the muscles you can control directly to move your skeleton.

If you are reading this and you are not a bird, you have smooth muscle controlling your iris. A mammal’s pupils dilate based on how much light there is in the room along with other factors that they can’t directly control, such as state of arousal. Pro-tip: if you’re playing with a cat whose eyes suddenly fully dilate, watch out — it’s no longer a game.

Pretty Little Dinosaurs

Birds, though, have skeletal muscle controlling their iris, which means they can dilate and constrict their pupil whenever they want to.

Pupillary dilation is a form of communication with birds, and you’ll often get a quick flash of the iris when a bird greets you or is excited about something. Watch this Amazon’s eyes as the owner is whistling to him.

Why Does It Matter?

That’s great, you say, but why do we care? As with so many other questions, the answer is “drugs”.

Drugs work very differently on smooth and skeletal muscle. That’s a good thing — if they didn’t, drugs to control asthma by relaxing smooth muscles in the airways might leave you paralyzed on the floor.

A bird under anesthesia doesn’t need to be able to fly, but it does need to breathe, and most of the muscles involved with breathing are skeletal muscles. If you use a drug to paralyze a bird’s skeletal muscles so you can work on the eye (during cataract surgery, for example), you’d better have a ventilator ready to go, because that bird isn’t going to be able to breathe on its own.

It’s fun to think about how cool it would be if humans could dilate or constrict their pupils at will, but it would certainly make eye exams a lot more difficult!

Links With More Information

Different types of muscle: https://medlineplus.gov/ency/imagepages/19841.htm

Everything you ever wanted to know about avian ophthalmology: https://www.vin.com/apputil/content/defaultadv1.aspx?pId=11147&catId=29502&id=3846255

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During Fun Facts Friday, I talk about something I think is interesting. Do you have questions? Suggestions for a future post? Add a comment below!

The easiest way to manage horses is to assume that they are trying to die from the moment they are born, and then make a plan to stop them.

Eat the wrong hay? Their gut stops working, they colic and die. Eat too much fresh grass? They get laminitis and their hooves can literally fall off. Too much calcium? They’ll build a stone in their gut and colic and die. Teeth don’t wear correctly? They won’t be able to eat right, then colic and die. Get their hooves trimmed incorrectly? Maybe they get laminitis and the foot rotates enough that the bone comes out through the bottom of the sole. They can even develop balls of fat on a stalk inside their abdomen which can then strangle their intestines leading to — you guessed it — colic and death.

But even before they can live long enough to get colic or laminitis, they have to survive the first few days after birth. And that’s where colostrum comes in.

The epitheliochorial placenta

The placenta is the uterine connection where nutrients and oxygen are transferred to the fetus, and byproducts such as carbon dioxide and ammonia are taken away. If you think about it, not only is mom eating for two, she’s also peeing for two. (Luckily the fetus isn’t eating much other than a bit of amniotic fluid, so there’s no need to poop for two because the placenta really isn’t set up for that.)

The basic idea of the placenta is that there are three layers of cells on the fetal side that match up to three layers on the maternal side. The maternal blood stays in the mother, the fetal blood stays in the fetus, things diffuse in both directions, and the fetus has everything it needs to grow and not poison itself.

In a human placenta (technically a hemochorial placenta), the three maternal layers are mostly gone, so maternal blood is making direct contact with the fetal layers. Because of that, maternal antibodies can cross over to the fetus during gestation, and when the human baby is born it is already protected from a lot of diseases.

Horses, however, retain all three maternal layers, leading to an epitheliochorial placenta. Antibodies can’t cross from the mother to the fetus. So when a foal is born, it has no protection at all from the bacteria in its environment. Eventually it will start making its own antibodies, but that takes a week or two to really get up to the point where it can fight off infection. And a foal is really not in a sterile environment when it is born.

The importance of colostrum

So if a foal can’t get antibodies during gestation, how does it avoid infection during the first week or two? The answer is that it receives the maternal antibodies during its first meal of colostrum, the first milk a mare produces, which is super high in antibodies.

For about the first twenty-four hours, the foal’s gut has special cells to absorb antibodies, so the antibodies in the colostrum pass into the foal’s blood stream, and then it’s ready to fight off infection. This is known as passive transfer.

Failure of passive transfer

Imagine all the things that can go wrong. What if the mare doesn’t produce colostrum with enough antibodies? What if the foal takes too long to figure out how to stand up and nurse, and the specialized intestinal cells are no longer around to absorb the antibodies? What if the mare dies and there’s no equine colostrum available? What if the horse gave birth unobserved and you’re just not sure if the foal got enough colostrum?

The good news is that it’s pretty easy to check the antibody levels in the foal with a simple blood test. If the levels are too low, the fix is a transfusion of plasma from an adult horse, which puts the adult horse’s antibodies straight into the foal’s bloodstream.

Over the next couple of weeks the maternal antibodies in the foal will gradually get used or destroyed, but at the same time the foal is starting to produce its own, so it is never left unprotected. With a little luck it will grow up and live a nice long life during which it tries new and creative ways to kill itself.

Want to know more?

Let’s face it — all I really wanted to know about reproduction in vet school was how to stop it, so don’t take my word for any of this!

Different types of placentation in mammals: http://www.vivo.colostate.edu/hbooks/pathphys/reprod/placenta/structure.html

More info about maternal antibodies: https://pubmed.ncbi.nlm.nih.gov/26507553/

And a good overview of the basics: Large Animal Internal Medicine, Bradford P. Smith, 3rd edition.

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During Fun Facts Friday, I talk about something I think is interesting. Do you have questions? Suggestions for a future post? Add a comment below!

Did you know one of the most common causes of blindness in dogs is cataracts caused by diabetes mellitus? In fact, it’s pretty much inevitable that a dog with DM will develop cataracts. But why does this happen in dogs and not cats?

Are you picturing Wilford Brimley yet?

Diabetes mellitus can be caused by a number of things, but the bottom line is the body either isn’t producing or isn’t using insulin, resulting in high blood sugar.

The sugar involved, glucose, is a small molecule and can diffuse through most cell membranes, so if there are high levels of glucose in the blood, there are high levels of glucose everywhere, including the fluid inside the eyeball. (There is also a lot of sugar in the urine, providing food for bacteria, so urinary tract infections are common.)

Glucose can be converted into sorbitol, but it’s a very slow reaction unless a catalyst (aldose reductase) speeds it along.

One important difference between glucose and sorbitol is that sorbitol doesn’t diffuse through cell membranes very easily. So if glucose gets converted to sorbitol somewhere, that sorbitol molecule is going to stay put.

What’s a lens and why does it matter?

Back to the eyeball — the lens (this page has a good picture of the anatomy of the eye) is a structure that sits in the middle of the eyeball and allows you to focus on things at different distances. It’s made from a bunch of fibers that are put together in such an orderly fashion that the final structure is crystal clear. If something damages that orderly structure, light gets blocked, which then impairs vision. A tiny cataract might just be annoying. If the whole lens is damaged, it will keep light from getting through at all.

[Related anecdote: One of my patients was an elderly bald eagle that came in from a zoo to have its cataracts removed. When it got to the hospital the bird just sat there, as if it were nighttime, and was easy to handle. Then we did surgery and removed the cataracts and suddenly it could see again. Bald eagles are big strong jerks with massive talons and I had to get medicine in that bird’s eyes twice a day over the weekend until we could send it back to the zoo. I definitely wasn’t getting paid enough for that.]

When lenses go bad

So the animal has diabetes and now there’s too much glucose everywhere, including inside the eyeball and even the cells of the lens. If the glucose molecules remain glucose, they will wander in and out and there won’t be a problem. But if the glucose gets converted to sorbitol, it won’t diffuse back out. More glucose will diffuse in, get converted to sorbitol and get stuck. Pretty soon it’s a sorbitol party, and then water gets pulled in. (If you don’t remember how osmosis works, just trust me on this part.) Once water gets sucked in, all the neatly arranged fibers of the lens end up all over the place, and now you have a full blown cataract.

Cats rule, dogs drool

Both dogs and cats can have diabetes, and both will have high blood sugar. So why do dogs get diabetic cataracts but cats don’t?

Remember the aldose reductase that helps convert glucose to sorbitol? Cats older than four years don’t have much aldose reductase in the lens, and cats younger than four generally aren’t diabetic.

Dogs, though, have a bunch of aldose reductase just sitting there in the lens, waiting to cause problems. The glucose diffuses in, gets converted to sorbitol, the sorbitol builds up, and bam! a few days later the dog is blind from an irreversible cataract.

Treatment

Cats: There’s no treatment for being a cat. You just have to accept them for what they are.

Dogs: As long as just the lens is affected, the whole lens can be removed and the dog’s vision restored. Without a lens they probably won’t be able to focus well enough to read the newspaper, but most dogs are okay with that.

If other parts of the eye besides the lens are affected, or if cataract removal is just not a financial possibility, the dog will remain blind. The good news is that blind dogs do very well. Some owners don’t even realize their dog is blind until they rearrange the furniture. My first dog was completely blind and she managed to get up to such shenanigans that I would have sworn she was sighted if her eyeballs hadn’t been completely removed.

So there you have it. Cats and dogs really are different. Want to read more?

• https://veterinarypartner.vin.com/doc/?id=4951531&pid=19239
• https://www.indyanimaleyeclinic.com/veterinary-information-network-publications/cataract-feline/

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During Fun Facts Friday, I talk about something I think is interesting. Do you have questions? Suggestions for a future post? Add a comment below!