Urinalysis

Hey Future Doctors! Thanks for joining me on Spoonful of Sugar, a podcast made for medical students, by medical students, to help the medicine go down. My name is Rhea, I'm a student at Druxel University College of Medicine, and I will be your host today. I am so happy that I decided to create this podcast, Spoonful of Sugar, because literally when else would I get an opportunity to publicly speak about urine. Spoiler alert, I'm not going into nephrology. You guys think I'm joking, but I'm actually really excited. In this episode, I'm hoping we can have a breezy review of the components of your analysis. We'll talk about dipstick, microscopy, we won't really touch on culture, but just acknowledge that that is something that you can order. Mainly, I'd like to start with talking about what we can see on urine dipstick, and then we'll talk about microscopy, specifically discussing different types of casts and stones, because those are the types of things you'll get tested on. As always, I'm going to be asking questions throughout, and so I'm really hoping that you guys will play along just for fun, and never get discouraged if you get something wrong, because the worst thing that can happen is you learn something. So when we order a urine analysis, there's different tests that we can perform on the urine. So in the outpatient setting, for example, if you're in a primary care office or in an urgent care clinic or often even in emergency room, the quickest thing that they can probably do to urine sample is get a dipstick. So what does a dipstick tell us? What information does it give? It gives a lot of things. It can give you the pH, it can tell you the presence of things like leukocyte esterase, nitrites, blood, protein. Again, it's not looking at specific cells. It's not looking at the red blood cells or the white blood cells, but it can detect the presence of blood. It can tell you specific gravity. If there's ketones, glucose, bilirubin, present, urine dipstick basically looks like a pH test. Those strips that you dip in liquid and they change color, that's basically what the urine dipstick looks like, except they change color for a lot of different parameters. So just generally, do you guys know what the normal pH of urine is? I think it's good to just have a general idea. It's about six. So it's good to keep that in mind that the pH of normal urine is about six when, especially further in our discussion, when we talk about stones, certain types of stones prefer acidic or basic urine. And so sometimes if a question stem gives you the pH of the urine, you can kind of keep that in mind. So let's say somebody gives a urine sample, you do a dipstick and it comes back with positive for leukocyte esterase and nitrates. What are you thinking of in this situation? A UTI, absolutely. And then if you were to perform microscopy and see bacteria growing there, you can actually order, when you order the test, you can order a reflex culture. And that can help guide the antibiotic choice for that patient. If there is blood in the urine, you do a dipstick, it comes back to plus positive for blood. What does that tell us? I think I should also note here that I'm talking about microscopic hematurio, okay, only detectable on the dipstick. It's not like they're grossly just peeing out blood. It's microscopic. What could it be? It could be several things. Hemorrhagic cystitis could definitely be something such as if a patient were to have a complicated UTI. There could be microscopic hematurio just from something like benign, prosthetic hypertrophy. It could be indicative of stones in the urine. It could even be indicative of malignancy in the kidney or in the urinary tract. Now, what if the urine dipstick were to show two plus blood, but there were no red blood cells counted per high-power field on microscopy. Again, there's two plus blood on dipstick, but when you actually look at the urine, there's no RBCs per high-power field. When would that happen in what situation? If you're thinking of rabidomyelitis, you're absolutely right. So in rabidomyelitis, the muscles break down and release myoglobin, and that can actually cause the dipstick to turn positive for blood, but you won't actually see red blood cells. I think this is a question that does come up several times. Let's get a little fancier now with our urine analysis. Say you're working in an effrologist's office. You might be on a dipstick. You might actually centrifuge the urine sample and look at it under the microscope. So what are things that we're looking for when we look at urine under the microscope? What do you think of? So as I sort of alluded earlier, you can definitely visualize white blood cells and red blood cells, and you'll see them count those cells per high-power field. So that just gives you an indication as to how many white blood cells or how many red blood cells are in the urine. Another thing that you might see are different types of casts, okay? So there's a lot of different types of casts, and they form in different conditions, and so they obviously make really great test questions. And so now it's time for a little rapid fire session kind of reviewing your knowledge of casts. So the first one, what if we were to see red blood cell casts in the urine? So it's actually very important to distinguish just the presence of red blood cells versus red blood cell casts. So if there's casts, then that indicates that the blood cells have actually had time to sit in the tubules and kind of mush together to form these rectangular shapes, right? And so that indicates that there's some type of pathology either in the glomerulus or in the tubules of the kidney. The red blood cells have had time to sit in the tubules and kind of conglomerate. So what are some conditions that would give us red blood cell casts rather than just generic red blood cells? Think of things like glomerulone fritis. There's blood leaking out through the glomerulus. This can happen in also in malignant hypertension, for example. And this seems like a silly question, but are red blood cell casts cellular or a cellular? They're absolutely cellular because they're made up of red blood cells. Now what about white blood cell casts? When would you see these? Anytime there's inflammation involving the tubules or the interstition around the tubules, white blood cells can kind of leak into the tubules and sit there and form some casts too. So can you think of a condition where you might see these? Pylone of fritis, acute pylone of fritis can definitely give you some white blood cell casts. If someone were to get a kidney transplant, these might also be seen in transplant rejection. Think of all the leukocytes going into the kidney to attack that organ. And again, silly questions, cellular or a cellular? White blood cell casts are absolutely cellular. How about fatty casts? These are sometimes described as oval fat bodies. When do you see fatty casts? This is interesting. You see these in nephrodic syndrome. Why would you see fatty casts in nephrodic syndrome? So remember the pathology of nephrodic syndrome. It actually causes a loss of proteins. And so one of the proteins that you lose in nephrodic syndrome are lipoproteins. And that can lead to lipiduria. Besides nephrodic syndrome, can you think of another rare situation where you might get fatty casts in the urine? Think of fat kind of going everywhere to the blood vessels. Fat embolism, okay? So nephrodic syndrome and fat embolism, those can both lead to fatty casts. Now, if you were to look at an oval fat body under polarized light microscopy, they have a really special appearance. And there's a name for it that you need to know. Do you know it? That would be the multis cross configuration. Have you heard of that? The multis cross sign? Those are seen when you look at oval fat bodies under polarized microscopy. And it has to do with the birefringens of the structure. If you're not able to visualize that right away, now or at some point later on, I would definitely recommend googling that multis cross sign. So you're familiar with it. Are fatty casts cellular or ac cellular? These are the first ac cellular casts that we've discussed. All right, the next one, granular muddy brown casts. When do you see those? So the granular muddy brown casts are actually pathonomonic for acute tubular necrosis. That is a condition that can happen anytime there's ischemia or toxic injury to the kidney. So there will be an episode further on about different types of kidney injury, but just remember that acute tubular necrosis is associated with granular muddy brown casts. Are these cellular or ac cellular? So these are actually cellular. These casts are made up of the epithelial cells which actually slough off into the tubules and kind of sit there for a while. And so So it's these necrotic epithelial cells that create that granular muddy brown appearance of the cast. What about waxy casts? When do we see these? They're sometimes described as broad waxy casts, if that helps, I don't know. So these waxy casts are a type of acelular cast, and they're also called renal failure casts because they form in diseased kidneys. The reason they form is because the kidneys are diseased, they're not moving as well, and so they form as a product of stasis. The ducts actually get kind of dilated as well, and that's why they tend to be more broad than other types of casts you might see. So when you hear the word waxy casts, think of renal failure casts, okay? Kidney is severely diseased. And then finally, I want to ask about hyaline casts. So hyaline casts are actually a normal finding, okay? If you see these, you shouldn't be alarmed at all. And they're actually made up of a normal protein that's secreted by the tubular epithelial cells. Do you guys know the name of that protein? If you do, I'm definitely impressed. This is the Tam Horse Fall Protein, okay? It's a normal glycoprotein that is secreted into the urine, the Tam Horse Fall Protein. And that's really what makes up the hyaline casts, which are also a completely normal finding. Good job, guys. I think it's great to be familiar with the different types of casts. And as long as you understand that they form from either cells or some other type of material sitting in the tubules for a long period of time, I think you're pretty much set. I'd like to move on now to a discussion about different types of stones that we might observe in the urine. And this is really going to be the meat of our discussion, this is probably where the most test questions come from. So first off, I just want to ask you guys, do you know how a patient with kidney stones usually presents? If you've ever had them, you know, or even if you've seen a patient, honestly, but these patients are insignificant discomfort. They have a lot of abdominal pain. It's described as callicky. The patient can't really get comfortable. They keep moving around. They won't stay still. They have this unilateral flank tenderness, and it usually radiates down to the groin. So men with kidney stones can actually complain of scrotal or penile discomfort as well. And patients may also have some hematuria associated with these stones. So these patients are really uncomfortable. And there are a presentation as sort of classic, okay, that unilateral flank pain radiating down to the groin. So what I'd like to do is describe some stones as seen by light microscopy. And after you guys identify what type of stone I'm talking about, we can kind of further discuss the pathogenesis and treatment of each. So the first stone I'm going to describe for you is the most common type of kidney stone seen, you know, over 80% of patients with kidney stones have this type of kidney stone. It's described as an envelope or dumbbell shaped stone, and it likes to precipitate an acidic urine. So urine whose pH is less than 6. What type of stone am I thinking about? Unvolved, dumbbell shaped, most common precipitates an acidic urine. This is a calcium oxalate stone, okay, calcium oxalate are the most common types of kidney stones. Do you guys know what causes these? There's a classic toxic ingestion that causes these. That would be ethylene glycol ingestion. So interestingly, I was reading about this, calcium oxalate stones are seen actually much further down the road after the early symptoms. So there's the initial symptoms that are similar to alcohol poisoning when someone takes ethylene glycol. And then about 24 to 72 hours later is actually when you would see these kidney stones. The reason they form is because glycolic acid gets metabolized to oxalic acid, basically as part of metabolism of ethylene glycol. And so the oxalic acid can then bind calcium and end up precipitating as stones. So one cause of calcium oxalate stones is ethylene glycol ingestion. What are some other causes you can think of? Hypo citrateria is one of them, okay, less citrate in the urine. And why would that be? Citrate normally actually binds calcium and it forms a soluble compound. If there's no citrate, then calcium is free to bind oxalate and that's not soluble. And that's why we'd form these calcium oxalate stones. Another cause of calcium oxalate stones. This one's weird. Overconsumption of vitamin C. Why would that cause calcium oxalate stones? Vitamin C. So what also has to do with the metabolism? So a scorbic acid or vitamin C in excess is excreted by the body as oxalic acid. And so excess of oxalate forms calcium oxalate stones. And you're kind of starting to see a pattern here. Anytime there's too much oxalate, we end up getting calcium oxalate stones. There's finally another cause of calcium oxalate stones I want to talk about. And it's an inflammatory bowel disorder. Can you think of one? Crohn's disease. Why would patients with Crohn's disease get calcium oxalate stones? I think this is the most interesting pathogenesis. So patients with Crohn's disease have malabsorption of fat and normally fat binds to calcium. So if the patients are not absorbing fat, then fat in the lumen of the intestines will end up binding calcium. And so the oxalate on its own ends up getting absorbed into the intestine. When the oxalate is absorbed in the intestine, it ends up entering the kidney finally informing calcium oxalate stones there. Does that make sense? Patients with Crohn's have malabsorption of fat. And so instead of calcium binding oxalate in the lumen of the intestine, the calcium in the intestine ends up binding the fat. So the oxalate on its own can end up being absorbed. And then through the bloodstream, it travels to the kidney where it forms calcium oxalate stones. I just wanted to say that again because it's a little bit complicated. If you understand it, I think it's really interesting. So just to summarize, the causes of calcium oxalate stones are ethylene glycol ingestion, hypocetrateria, excess vitamin C, and Crohn's disease. And I tried to spend time going over the mechanism of the stone formation because otherwise these are seemingly random causes. And it's kind of difficult to just memorize them. But I think if you understand why they cause stones, it makes a lot of sense. Now a question you might get asked is what are the calcium levels in the blood of patients who form calcium oxalate stones? Would you expect them to be high? The answer is actually no. Patients with calcium oxalate stones are usually normal calciumic, but they just have hypercalci urea. So you would not expect if you were to check their blood for calcium, their levels would not be elevated, they are normal calciumic with hypercalci urea. Now what is the treatment for calcium oxalate stones? How do we treat these? I think the mainstay of treatment in the supplies not just for calcium oxalate, but for all stones. The biggest thing is hydration, just try and drink as much water as possible, try and dissolve the stones, and hydration is really used to treat any stones that are less than 5 millimeters. Patients who have larger stones, greater than 5 millimeters, they often need a urology referral, and urology can either use lithotripsy or if they are really big they might need surgery. But most of the time stones are going to be small enough that hydration can just be the mainstay and you wait for the patient to pass the stone. Now what if a patient has hypertension and they also have a propensity towards forming kidney stones, specifically calcium oxalate stones? That might be a good diuretic to place them on. So psiosides, psioside diuretics actually cause absorption of calcium. So they end up removing calcium from the tubules and psiosides as a side effect cause hypercalcemia. But in this case that's a good thing because that means we're removing calcium from the tubules and so we're less likely to form these calcium oxalate stones. So hydration, diazide diuretics, and what about dietary changes? Are there any dietary modifications we can make to prevent calcium oxalate stones if our patients were to ask us? Absolutely. So one thing I want to point out is that lowering calcium in the diet actually does not help. Okay. In fact, if we have lower calcium in the diet then we'll have increased absorption of oxalate in the intestine, more oxalate in the blood, and that can end up in the kidney. Think of the mechanism for how patients with Crohn's disease get these stones. So lowering calcium is actually the wrong answer. Interestingly though, one change to the diet that can help is lowering sodium. Do you guys know why? I think it's sort of tricky. There are studies that have shown a link between high salt, diet, and nephrolethysis, and I think it's postulated that it might have to do with how salt and calcium are both handled in the proximal convoluted tubule. So their absorption is sort of paired, and high sodium actually decreases the efficacy of sodium reabsorption channels, and so that also leads to less effective reabsorption of calcium. So you end up getting more calcium staying in the urine, and then a more increased propensity towards forming these calcium oxalate stones. I hope that makes sense. So besides calcium oxalate, calcium can also combine with a different element to form a different type of stone. This one is shaped like a wedge or a prism. Do you guys know what I'm thinking of? This would be calcium phosphate stones, okay? Do you guys know if calcium phosphate stones are radial opaque or radial lucent? These are radial opaque. Most stones are radial opaque. And do these guys like a high or low pH? They like a high pH. So remember that calcium oxalate precipitated in acidic urine. Calcium phosphate likes alkaline urine. And how would you treat these? Clearly, thizides, low sodium diet, okay, and of course hydration. The next type of stone I want to talk about forms a radial opaque coffin-shaped crystal. And this commonly actually presents as a giant staghorn calculus in the renal pelvis. Do you know what stone I'm thinking about? Giant-shaped crystals and then they form staghorn calculi in the renal pelvis. I'm thinking of streu-vite stones or ammonium phosphate magnesium stones. These guys are kind of interesting. Do you guys know what predisposes patients to form streu-vite stones? It's infection with specific bugs. Do you know the bugs? They are proteus, merabolus, staph, saprophyticus, and clebciella species. So proteus, staph, saprophyticus, and clebciella. Why would these predispose to forming ammonium phosphate magnesium? These organisms all actually hydrolyze urine to form ammonium that alkalizes the urine and it makes you likely to form ammonium phosphate magnesium stones. So again, these type of stones, in addition to the calcium phosphate stones we discussed earlier, they both like alkaline urine. What is the treatment for these streu-vite stones? Obviously, you'd want to give antibiotics for the bugs if that's the cause of these stones, but to remove the stone itself, they're actually so large that they often need to be treated surgically. The next type of stone I want to discuss is a radio loosened stone, and this one will form rosettes or rhomboid shapes, and it might be seen in patients who have gout. What kind of stone is this? I think the gout is a real giveaway. These are uric acid stones. Do you guys know what type of pH these like? They like acidic pH, lower than 6. And then besides gout, can you think of another condition where we might see uric acid stones? Just think of another condition where you'd have increased uric acid. I'm thinking of leukemia, but really it's any time that there's increased cell turnover. Uric acid is a product of purine and pyromidine metabolism, so any time that cells are actively replicating and turning over very fast, you'll have increased uric acid. So leukemia is definitely one of those situations. You can also think of something like tumor lysis syndrome where patients with cancer, such as leukemia, are treated with chemotherapy agents, and then their cells just break open and release uric acid everywhere. So gout leukemia. And how do we treat uric acid stones? One thing we can do since they do like acidic urine, we can alkalize the urine to prevent their precipitation. And you think of a drug that we can use to prevent increased levels of uric acid? Halopurinol. How does halopurinol work? It inhibits the enzyme xanthine oxidase, think back to biochemistry. And so that directly inhibits uric acid formation, because remember xanthine oxidase is involved in kind of that degradation pathway, which ultimately leads to uric acid. So alopurinol inhibits that enzyme, and it can be used to help prevent uric acid stones in addition to preventing gout. Now what is a drug that's used to treat gout that you'd absolutely want to avoid in someone who has a history of uric acid stones? I'm thinking of the drug probenicid. So the mechanism of probenicid is actually to inhibit reabsorption of uric acid in the proximal convoluted tubule. And so if it inhibits reabsorption of uric acid, it can also actually precipitate uric acid calculate, because all that uric acid is just sitting in the tubules then. So for patients with uric acid crystals, alopurinol is a good treatment, and it also helps with their gout. And if they have gout in uric acid crystals, you want to avoid probenicid, because that can encourage the formation of these stones. And then finally, the last type of stone I want to discuss is usually seen in children. It also precipitates an acidic pH, and this one is shaped like a hexagon, and it's described fairly as a fairly radio opaque. You guys know what stone I'm talking about? A hexagonal shape, acidic pH, usually seen in children. Oh, and fun fact, it can also form staghorn calculi. I am thinking of cysteine stones. So cysteine stones are actually very rare. They're not seen often at all, but they're associated with a genetic defect. Do you guys know the condition? It's an autosomal recessive condition, and it is a defect in the transporter that's found in the proximal convoluted tubule, which is responsible for absorbing cysteine. And in addition to cysteine, it's also responsible for absorbing ornithine lysine and arginine. So these four elements together, cysteine, ornithine lysine, arginine, COLA. I call it the COLA transporter, there's a specific condition, which is autosomal recessive, and patients have a defect in the transporter to reabsorb these. And so they have more cysteine in the urine, and they can actually get cysteine stones. Do you guys know how we might treat these? So again, cysteine stones like acidic urine, so we can just alkalize the urine. A low sodium diet can help, and if necessary, we use chelating agents. That was definitely a lot of information. And so I just want to give you guys some pointers, things that I used to stress over a lot, that in retrospect, I realized I didn't have to stress over them that much. Most stones are going to be radio opaque, okay? I used to spend so much time wondering like, oh my god, is it radio opaque? Is it radio loosened? Most stones are radio opaque. All that means that they are dense and they darker, they're darker, and they do not really allow light to pass through them. There's only one real exception, and do you remember what that is? It's uric acid. Uric acid is the only radio loosened stone, and I just remember that because uric acid and radio loosened both have that u sound in them. So uric acid, radio loosened, and the rest are just going to be radio opaque. And then the second thing I used to stress about is the pH of the urine, but you don't have to stress about that either. Most stones are going to precipitate an acidic urine when the pH is less than 6. There's only two exceptions that we discussed. Do you remember them? So calcium phosphate and ammonium magnesium phosphate are the streuvite stones. These are both the stones with phosphate in them, so just remember phosphate or you can remember mag and phosph, these are two electrolytes we often commonly check together. So just remember mag and phosph, and these are the two stones that precipitate in alkaline urine. To be honest, you really don't need to stress about the radio loosened C and the pH of these stones, because usually in these questions, the vignette is fairly straightforward, and it will help you get to the answer with other clues regarding risk factors or the epidemiology of these stones. But I just think it's easy to remember. There's only one radio loosened stone, and it's uric acid, and there's only two stones that like alkaline urine, calcium phosphate and ammonium magnesium phosphate. And that about sums up everything that I wanted to talk about regarding urinalysis. We discussed some of the components of dipstick, as well as microscopy, and within microscopy, focused on different types of casts and different types. of stones. And so, really quickly before we close, I just want to do a rapid fire, question, an answer, and then we'll wrap up. So, just a few questions for you guys. If you see nitrites and leukocyte esterase positive in the urine of a patient who complains of dysiorea, urgency, frequency, what's the diagnosis? Urinary tract infection, absolutely. What if the urine dipstick shows 2+ blood, but microscopy shows no red blood cells per high-power field? This is rabdo myalysis. Think rabdo. Now, can you guys remember two situations with fatty casts or oval fat bodies? What are two things we talked about where you would see fatty casts? Right, we talked about nephrotic syndrome as well as fat embolism. And what do these look like under polarized light microscopy? That classic, malteased cross sign. Google it if you can't remember what it looks like. When do we see broad, waxy casts? These are the kidney failure casts we talk about from dilation of the tubules and stasis of the kidneys. When do we see high lean casts? This is a normal finding. And what type of protein do they contain? What was that special name we talked about? That would be the tam horse fall protein. And what's the most common type of kidney stone? Over 80% of patients have this type of stone. Calcium oxalate, absolutely. And what diuretic would you want patients to be on to treat their calcium oxalate stones? Thiazides, these cause calcium reabsorption in the tubules. So thiazides for calcium oxalate stones. And finally, what were the two stones we talked about which precipitate in basic urine? Remember, mag and phosph. So the calcium phosphate stones and then the ammonium magnesium phosphate were the true white stones. Great job guys. If you survive that rapid fire review, you really know your stuff. So I just like to conclude by saying I think your analysis is a fairly straightforward topic. I think cast and stones can be difficult to memorize, which is why I tried to sort of highlight elements that you can try and understand rather than just regurgitate. I think if you understand why things like vitamin C, Crohn's disease, hypo citrateria, why these lead to calcium oxalate stones, it's really the pathophysiology that's important. The hardest part I think for me was just memorizing subtleties like what pH of these stones like, are they radio opaque or radio loosened? But as I said, this is honestly not the mainstay of board questions. This is not what they're going to trip you up on. There will always be other clues in the vignette to help you get to the right answer. So really don't stress about your analysis. Just enjoy what we've discussed so far. Thank you so much for your time today. I'm really glad I had the opportunity to talk to you about P. I hope you enjoyed listening to our discussion about P. If you have any questions, comments, concerns, please visit our website at spoonfullofsugar.org and you can post them there. And we'd be absolutely delighted if you could give us a rating or a review, subscribe to our channel. 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