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S2D: The Symptom to Diagnosis Podcast - Episode 20: Hematuria
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S2D: The Symptom to Diagnosis Podcast - Episode 20: Hematuria
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Language: EN.
Segment:0 .
[upbeat intro music] [upbeat intro music] [upbeat intro music]
DR. CIFU: I'm Adam Cifu.
DR. STERN: And I'm Scott Stern.
DR. CIFU: And we're here with another episode of S2D, the Symptom to Diagnosis podcast. This podcast teaches evidence-based strategies for diagnosing common medical symptoms. We begin each episode with a case unknown to one of us. We then discuss five high yield features that help to accurately diagnose the cause of the symptom at hand. We then return to our case before finishing up with a discussion of fingerprints common misconceptions, pet peeves, and other random pearls of knowledge pertaining to the week's symptom.
DR. CIFU: The cases that we discuss are drawn from our clinical experience, but because protecting patient privacy is part of our oath, we never discuss actual patients and most cases are composites. What are we talking about today, Scott?
DR. STERN: Today is hematuria day.
DR. CIFU: You know I actually knew that's what we're doing.
DR. STERN: I knew you knew that.
DR. CIFU: [chuckles]
DR. STERN: All right, so Adam, you are the expert of the day and I bet you have a case to present to me.
DR. CIFU: I do and in fact, I could have skipped that whole thing about patient privacy, because for the second time I will be presenting a case of my own health issue.
DR. STERN: Ah-huh!
DR. CIFU: You're ready for the case?
DR. STERN: Now I'm afraid.
DR. CIFU: Okay, I'm actually going to give you a little bit of the history today and I'm going to have you ask me some questions.
DR. STERN: Okay.
DR. CIFU: Okay?
DR. CIFU: So this is a 45-year-old man, a physician.
DR. STERN: [chuckles] I see this was some years ago then.
DR. CIFU: [chuckles] Yes, it was. And this man was vacationing in Hawaii with his family. He went on a long, beautiful walk in the morning. His kids actually complained that it was like the Bataan Death March was the words they used. [chuckles] After the hike, he drops off his wife and daughter so they can go horseback riding, this patient hates horseback riding. And then goes to a coffee shop with his son.
DR. CIFU: He drinks a large ice coffee, goes to the bathroom where he passes reddish brown urine. He hydrates well, sees no more blood for the duration of the vacation and then goes to his doctor three days after his return.
DR. STERN: Well that's fun.
DR. CIFU: Yeah.
DR. STERN: Okay, so let's see. The first thing that strikes me is two things, one, it's reddish brown. So it doesn't really sound like lower tract bleeding frankly, you know, bladder bleeding, blood clots really suggest bladder bleeding, but even without that, bladder bleeding tends to be red. So this could be glomerular bleeding or it could be something that's non-bleeding, I mean, the Bataan Death March certainly raises the question of either rhabdomyolysis or march hemoglobinuria which I've often heard talked about and never seen.
DR. STERN: So that would be interesting.
DR. CIFU: Right.
DR. STERN: Is he on-- And it never happened again, which is very interesting. So what medications is this patient on?
DR. CIFU: This patient was on no medications at the time. I think he uses like albuterol for asthma, no other medical problems, perfectly healthy guy, non-smoker and had no pain with the episode as well, non-smoker and had no pain with the episode as well, no burning, anything like that and noted no change in his urinary symptoms.
DR. STERN: Just discolored.
DR. CIFU: Just discolored, yeah.
DR. STERN: Right, so no frequency, no urgency, no fever, so UTI sounds unlikely. And again, I would have expected that to be red primarily.
DR. CIFU: Yeah, yeah.
DR. STERN: It doesn't sound like a stone given the color and the lack of pain, although I suppose it's possible. It doesn't sound like a malignancy given the nature of the color of the urine. I mean, what you would really want, and I have a feeling we can't get it now is to have known what the urine was at the time because I'd like to see frankly whether he has a positive-- The classic thing if he has hemolysis from marching would be that he has red urine that is dip positive but microscopy negative.
DR. STERN: And maybe a CPK just to make sure he didn't have rhabdo especially with the walking. But I suspect all those are going to be normal now. And then the question is going to be, if they're normal what do you do about this?
DR. CIFU: Right, right. And unfortunately this person does not carry urine dipsticks with him on a regular basis to do it at the time. Let me add one more little piece of history is that the night before this hike, patient went out, he had hamburger, French fries, and that night just felt some sort of diffuse and that night just felt some sort of diffuse I guess, non-specific belly pain still kind of felt that in the morning by the time the hike was over was sort of feeling fine, not really feeling that anymore.
DR. STERN: Hmm, so let's assume that that's significant and you're not just telling me that for no reason--
DR. CIFU: That would be cruel.
DR. STERN: And so what would that make me think if there was something going on in the gastrointestinal tract, could he have some sort of associated glomerulonephritis that's showing up. sort of associated glomerulonephritis that's showing up.
DR. CIFU: Interesting, yeah, he could.
DR. STERN: But I'm not exactly keying in on what that might be, so--
DR. CIFU: So let's leave it there.
DR. STERN: Okay.
DR. CIFU: This is, as I was saying, this is cruel because this is like the most atypical presentation ever of something really obvious. So, I'll--
DR. STERN: You'll stop torturing me and just--
DR. CIFU: I will stop torturing you and I will recognize that there will probably be some comeuppance at the end of all of this.
DR. STERN: [chuckles] At least in a different case. Okay, so let's get into a deep dive. And I think you're going to start us off with five key points about diagnosing hematuria which I have to say gets everybody's attention when they see blood in the urine they're in your office quickly.
DR. CIFU: Oh my God, absolutely. I remember actually seeing a movie when I was like in middle school where someone had hematuria in the movie and I was like freaked out and had to leave the movie theater. So as usual, you've touched on many of my five key points already, just as you sort of thought through this case and talked out loud. So point one is that not all red urine is hematuria.
DR. CIFU: There are sort of two important things. There is pigmenturia which is where the urine just turns red but has nothing to do with blood at all. I think the most common things I think about that is beets, like I see that all the time during the summer someone goes to the farmer's market, is all excited, buys a bunch of beets, and then their urine turns red. Usually their stool turns red the next day, too.
DR. CIFU: Medications, rifampin I think being the most classic, and then phenazopyridine, Uristat, as you know bladder anesthetic kind of classically turns the urine red. And then there are also substances which turn the urine red and cause for a positive dipstick for blood, but without red cells. And you mentioned this already and that's hemoglobin as with hemolysis or myoglobin as with rhabdo.
DR. STERN: Yeah, the other drug substance I was thinking about as you were talking when you mentioned your GI problems is bilirubin. Now bilirubin often looks, I would say orange, orange to brownish. So if you were throwing me a real curve ball which I'll beat you up for later, would be-- [chuckles]
DR. CIFU: [chuckles] Yeah.
DR. STERN: --bilirubin in the urine, but you know, we often talk about this, I have to say, we'll see what this case is, aside from this case, have you seen myoglobin or hemoglobin show up in the urine in all your years of practice and not from red cells?
DR. CIFU: So I have seen myoglobinuria--
DR. STERN: You have?
DR. CIFU: --but at the time
DR. CIFU: that was in no way a diagnostic dilemma because it was a couple of patients who were presenting with rhabdo. Actually, the most interesting case I saw that is someone who had terrible Legionella pneumonia and had rhabdo related to Legionella infection and had rhabdo related to Legionella infection and had myoglobinuria related to that.
DR. STERN: You know, worldwide rhabdomyolysis is the most common cause of renal failure from earthquakes.
DR. CIFU: Interesting.
DR. STERN: So people get crush injuries and release all this myoglobin and then have renal failure.
DR. CIFU: Right. Well, you actually see-- This is going to be one of those podcasts, we get way off the subject, but that's okay, it's going to happen every now and then. I've actually seen sometimes films of rescuing victims from collapses and when things are done well, like if they're working on freeing someone, but don't have them out yet, they will throw in an IV and alkalinize them with the idea that as we're digging this person out, we'll try to save their kidneys.
DR. STERN: Wow, that's impressive.
DR. CIFU: Yeah, yeah.
DR. STERN: All right, the second point.
DR. CIFU: The one other thing I wanted to mention, you had mentioned march hemoglobinuria. I imagine we probably won't get back to that just for people who don't know what that is, I think the idea of that is you actually get hemolysis just from sort of red cell sheer as they kind of course through the muscles in your lower extremities, which are super active. That's about right.
DR. STERN: I think that's right.
DR. CIFU: Second key point. So when I think about the hematuria differential I really think about organizing it by anatomy. Okay? And some of the structures in the anatomy are more likely, or some of the abnormalities in the anatomy are more likely to cause gross hematuria, some more likely to cause microscopic hematuria but either way, the workup is about the same, and so I'll be talking about that altogether. My third key point is let's get into the differential and the first real pivotal point and Scott, again you mentioned this, is the hematuria glomerular or not, okay?
DR. CIFU: Glomerular hematuria will have some classic findings. And those are dysmorphic red cells in the urine and maybe red cell casts and glomerular hematuria may also be associated with things like hypertension, proteinuria, acute kidney injury, if you have glomerular nephritis going on at the same time. Other causes of hematuria, so non-glomerular causes of hematuria usually just have red cells in the urine.
DR. STERN: And this is a little tricky if there's a fair amount of blood because if you have a fair amount of blood, then sometimes because blood is leaking and you do get some protein but I don't think I've ever seen like 3 or 4+ protein in the face of non-glomerular bleeding.
DR. CIFU: Right, I agree with that. I'm going to sort of stay away from glomerulonephritis because glomerulonephritis has sort of freaked me out since I was a second year medical student I, like, read Robbins, and I was like, "I can't learn this stuff." And to be honest with you, it really is mostly the purview of the nephrologist, but just to throw out some common causes, if you're talking about isolated glomerular hematuria, so basically glomerular hematuria without a lot of other problems going on, IgA nephropathy, Alport syndrome, thin basement membrane, nephropathy are common.
DR. CIFU: And then common cause of real glomerulonephritis, post-infectious, SLE lupus, or certainly in the hospital, HUS TTP.
DR. STERN: And HUS is associated with some of the GI infections, isn't that?
DR. CIFU: Right, so you can imagine that this person, maybe they went to, what was it? It was jack in the box that had outbreaks of E. coli--
DR. STERN: Like Campylobacter, Salmonella, Shigella and just happening to see this after they're marching.
DR. CIFU: Exactly.
DR. STERN: That would be cruel
DR. STERN: but definitely on the list.
DR. CIFU: I think actually also if it had happened to be you would have known about it, right? Because it would have been such a great story. I would have told you 20 times by now.
DR. STERN: Probably so.
DR. CIFU: Fourth key point. Most of the time, the cause of hematuria will be infection, stones or tumors of the kidney, ureter, bladder or prostate. Okay? Most of those being urothelial, right? Kind of kidney or bladder. Workup should certainly be guided by demographics of the patient, you know, is this a younger patient? Is this an older patient? And symptoms, is this one episode of gross hematuria with nothing else?
DR. CIFU: Does the person have kidney stone pain? Does the person have infectious symptoms? But in the end, you work it up, if you find something based on the history and physical, great, if you don't though every patient should sort of end with a CT urogram that's a pre and post-contrast, abdominopelvic CT and cystoscopy to make sure you've really cleared the entire urinary tract.
DR. CIFU: There are really excellent commonly updated guidelines on the evaluation mostly of microscopic hematuria. The most recent one is from the AUA, the American Urological Association.
DR. STERN: I have been struck by how much bladder cancer I see in my clinic, this is not an uncommon problem. This is a common problem. You get an older man who has hematuria and it is all too often bladder cancer. So those guidelines are spot on, we're not talking about a rare phenomenon here.
DR. CIFU: Right, right, and the good thing is that a lot of bladder cancer presents very early. If you respond appropriately to microscopic hematuria or gross hematuria, you'll find it when it's, you know, whatever epithelial, right? And there's no invasion into the muscularis and that's an easy tumor to treat.
DR. STERN: Right. All right, so you have one more point for us.
DR. CIFU: Fifth and final cause I'm going to throw out a couple of, I don't know, if they're zebras but just things that we don't talk about very much. There are some uncommon renal causes of hematuria. There are some uncommon renal causes of hematuria. I think when I think about renal cause of hematuria I'm mostly thinking about, is this glomerulonephritis or is this like a renal tumor or stone but things that you actually see occasionally are polycystic kidney disease, papillary necrosis which I think we probably see the most in people with sickle cell disease and even renal vein thrombosis.
DR. CIFU: You know, it's not a common problem but it's not like a one in a million kind of thing.
DR. STERN: So let's go back to our case. I'm kind of curious. So can I ask you for his physical exam and then some tests? So you're seeing him three weeks later--
DR. CIFU: Three days later.
DR. STERN: Three days later. Oh, I thought it was weeks. So three days later, so his vital signs?
DR. CIFU: Vital signs are normal. He's feeling absolutely well at this time though he says he still has a little bit of, kind of vague abdominal discomfort but your abdominal exam is completely normal.
DR. STERN: And is that diffuse or localized abdominal discomfort?
DR. CIFU: His discomfort, he says it is primarily right-sided.
DR. STERN: Primarily right-sided, okay. Is he having any fevers?
DR. CIFU: No fevers.
DR. STERN: No rebound, no guarding.
DR. CIFU: No rebound, no guarding.
DR. STERN: Upper or lower right side?
DR. CIFU: It's upper and maybe a little bit towards the side and maybe even all the way around to the flank.
DR. STERN: Oh really?
DR. CIFU: Yeah.
DR. STERN: So right-sided upper abdominal pain to the flank, so now we're talking about either in the right kidney or in the gallbladder again, just dark urine. All right, I need to see some labs on this fellow.
DR. CIFU: Okay. So his labs are completely normal. CBC normal, CNP is normal, UA interestingly was positive for blood, 1+ blood, no red cells. And that's all you got.
DR. STERN: But he's tender. This is peculiar. So, I don't actually know what I'm dealing with. I kind of know what I might do next, but I don't know. So, I'm not always convinced when they don't see red cells that the cells just didn't lyse. So the classic teaching on this is, this is hemoglobinuria without red cells, but red cells can lyse in a dilute urine. And so probably the most common cause of heme positive, red cell negative urine is just lysis of red cells, not really hemolysis.
DR. CIFU: Especially, in a physician who has been drinking a ton because he was freaked out by seeing the hematuria. He didn't really want to see it anymore and had some wild, crazy thinking--
DR. STERN: So I guess I would probably get an ultrasound look for a stone in this situation.
DR. CIFU: Okay. So what happened? You are right on to your colleague who saw me, who was thinking the exact same thing who scheduled me actually for a CT urogram, followed by a cystoscopy. This was a Monday, two days later before the CT scan, This was a Monday, two days later before the CT scan, I go for a run and I come back and once again have gross hematuria. I get the CT that afternoon and I've got a five millimeter stone in my proximal ureter just stuck there.
DR. STERN: And that's all the pain that you were in?
DR. CIFU: That's it.
DR. STERN: You don't know how to read a book to save your life?
DR. CIFU: I know, I know,
DR. CIFU: did I escape it beautifully?
DR. STERN: It's mostly abdominal, maybe a little bit in the flank?
DR. CIFU: Yeah.
DR. STERN: I have to say, you're the only person I've ever heard who presented primarily with abdominal pain from a kidney stone.
DR. CIFU: Yeah, yeah and I think I just got off so easy because I was like, it was pain that I would just blow off and I wouldn't even pay much attention to it. Well, usually when you see people with kidney stones, it's up there with, you know, childbirth, right? Just like some of the worst pain--
DR. STERN: A bad type pain--
DR. CIFU: Right, right.
DR. STERN: Well, I can promise you if I ever have a kidney stone, I will present classically rolling on the ground with pain.
DR. CIFU: It's funny, I was so relieved when I got the CT result back because at that point I was like, "Well, I clearly have renal cell carcinoma." And so I was thrilled when I heard that I had a stone.
DR. STERN: And why when you're running, is this happening?
DR. CIFU: I think what happened is that it was there, It was not doing anything, not creating a whole lot of problems. Go running for four miles, jiggle it around a whole lot, roughed up the ureter and started bleeding, I don't know. A lot of hand-waving there.
DR. STERN: All right.
DR. STERN: All right. So let's go on to fingerprints, common misconceptions, pet peeves, and other random pearls of knowledge. I do have to say it only proves that it's much more common for common things to present uncommonly than uncommon things. So this was a classic presentation of march hemoglobinuria, which it wasn't.
DR. CIFU: Right, right.
DR. STERN: Right?
DR. CIFU: Exactly, exactly.
DR. CIFU: And kidney stones probably, I don't actually know what the numbers are, I'm sure we don't even know what the numbers are, that if you take all comers with gross hematuria stones that if you take all comers with gross hematuria stones have to be near the top, if not at the top.
DR. STERN: Yeah, maybe just behind infection.
DR. CIFU: Right.
DR. STERN: All right.
DR. STERN: So do you have some fingerprints?
DR. CIFU: I don't.
DR. STERN: Me neither.
DR. CIFU: [chuckles] Okay, let's move on.
DR. STERN: Common misconceptions.
DR. CIFU: Okay. Common misconceptions. This may be an obvious one but I think it's important is that hematuria is okay, or is not that worrisome or can be passed over if a patient is on anticoagulation, that's just not true. Hematuria is abnormal, even if your patient is on, I don't know, warfarin or rivaroxaban or whatever, if they have hematuria, you got to work it up. There's a super old study, it's actually, I looked it up just before this to remind myself when it was from, it's from the Archives of Internal Medicine, now JAMA Internal Medicine, from 1994.
DR. CIFU: It's a wonderful study that took 243 patients followed them prospectively for two years, and what they found out is that the incidents of hematuria was no different in people who were anti-coagulated at that time, obviously it was on warfarin versus controls. And that when people did have hematuria and you work them up 81% of the cases actually had like a real cause, all the things that we've talked about so far.
DR. STERN: So kind of similar to GI bleeding and anticoagulation, you'll still work it up.
DR. CIFU: That's exactly what I was thinking. And also similar to when we talked about the data behind people with benign sounding rectal bleeding, anorectal bleeding is you still have to take it seriously.
DR. STERN: It worries me that 1994 seems like you said it was a long time ago, that doesn't feel that long ago to me [chuckles] but maybe that's just-- I'll let that go. All right, so my common misconception is I have a little bit been confused about when we talk about blood clots in the urine. So the common teaching, which is true is that blood clots represent lower tract bleeding but you have to be careful that that still includes all of the uroepithelium going up all the way into the renal pelvis.
DR. STERN: So it's easy to-- When you hear blood clots you're not thinking about glomerular bleeding, that is true, but renal cell carcinoma, kidney stones, bladder cancers can all present that way. And the point I want to make is you still have to image the kidneys in addition to the bladder if you don't find the source in the bladder.
DR. CIFU: Right, I agree, I agree. And I have a fairly memorable case from decades ago And I have a fairly memorable case from decades ago of someone who presented maybe the worst hematuria that I've ever seen with clots, with obstruction related to clots was from renal cell carcinoma which, I guess, had acutely eroded into a vessel to cause that.
DR. STERN: All right, and you have another one?
DR. CIFU: Yes, I would say maybe I'll build on what you just said. And I would say that gross hematuria is very scary and looks terrible, but it never really represents like significant life-threatening blood loss. It's not an upper GI bleed where someone can exsanguinate, people don't really exsanguinate out of their urinary tract. The cause may be significant, you know, it may be cancer but it's probably not going to kill them acutely. Probably the greatest risk of heavy bleeding is what we've already referenced, is that you clot off a ureter or you clot off even more worse in the urethra and can get renal injury related to that.
DR. STERN: I did have a fellow who once got urinary tract obstruction from bleeding. And so the next time he bled, he drank so much water he got hyponatremia and seized.
DR. CIFU: [chuckles] I think you've told me about that--
DR. STERN: I have. All right, so let's go into pet peeves.
DR. CIFU: Okay, pet peeves. This gets a little bit to what we've always talked about when you have someone with gross hematuria or let's even say microscopic hematuria, skipping the cystoscopy after a normal CT, because it sounds like a terrible test, okay? This is, I think maybe this is a bias, but for me it's usually in my male patients are like, "Oh my God, I'm not doing that." And that's just wrong.
DR. CIFU: You mentioned how common bladder cancer is. And the data that I have for this is that if you look at all the urothelial cancers, 90% of them are in the bladder. So if you've worked up urothelial cancer without evaluating the bladder, you've missed 90% of the tumors.
DR. STERN: Right, it's like when you look at the colon you can't really look at the colon with the CT scan. You have to look at the lumen, right?
DR. CIFU: Right, perfect.
DR. STERN: Okay.
DR. STERN: So mine was, you still have to evaluate hematuria, even if it resolves spontaneously. You know, there was a study that showed that if they took men who are over 50 who had intermittent hematuria, upwards of almost 10%, 8 to 9% of them actually had a urinary tract malignancy when they were evaluated. So it's tempting to say, and patients always want to do this when they have microscopic hematuria or gross. "How about if I see if it happens again?" And the proper response to that is "No", because you might be sitting on something that's blood once and it's your opportunity to diagnose the cancer early.
DR. CIFU: Right, right. Terrific point. And I think that is certainly reflected in the guidelines. And what's complicated is that, you do have patients who have benign chronic microscopic hematuria but you really can't say that until after you've evaluated them.
DR. STERN: Right, and then you can stop, then you don't-- Right?
DR. CIFU: Right.
DR. STERN: All right, so let's go on to some clinical pearls. I think you have a couple.
DR. CIFU: Clinical pearls, and again, you sort of referenced this, or alluded to this earlier. You know, we always talk about a positive dipstick for heme that's negative for red cells. And we sort of jump on that as saying this is hemoglobinuria or myoglobinuria. There are a few other causes. I was very impressed, you named one of these which is a very dilute urine actually causes osmotic lysis of almost all the urinary red cells, so although your positive dip is from red cells, you're not seeing red cells because you've lysed them.
DR. CIFU: A few other causes, so interestingly semen may cause a positive heme reaction on the dipstick. I don't think that's very common but if someone has had recent ejaculation and therefore has some semen left in their urine that could cause a positive dipstick. Alkaline urine, but it's really alkaline urine, pH greater than nine.
DR. STERN: Wow.
DR. CIFU: Contamination with oxidizing agents used to clean the perineum can cause a positive dipstick. And lastly, we never talk about a negative dipstick with a positive micro and that's because actually the dipstick is so sensitive. The dipstick is generally said to pick up two cells in the urine, and a positive micro is three to five cells. So actually the dipstick is more sensitive than the micro.
DR. STERN: Right, right. Well, that's terrific. And the only clinical pearl I would add to that is that you really have to routinely check a urine culture on any patient who has hematuria because it's actually fairly common that urinary tract infections will present with blood.
DR. CIFU: Yeah, you should almost just repeat that.
DR. STERN: Just do it.
DR. CIFU: Right, and the fact that we got to the end of this podcast without really hammering that home, maybe it's terrible because it really is true.
DR. STERN: [chuckles]
DR. CIFU: And you'll sometimes be surprised that people will come in with hematuria that you're like, "That doesn't sound like cystitis," but it ends up being cystitis. And the flip side of that is a lot of patients will come in, absolutely freaked out by the blood and will have to be reassured that like, cystitis causes blood and we treat it the exact same way we treat cystitis without blood. So let's just treat it.
DR. STERN: Absolutely.
DR. CIFU: So we hope you found this episode of the Symptom to Diagnosis podcast useful and a bit enjoyable. As a reminder, our textbook, Symptom to Diagnosis: An Evidence-Based Guide takes a much deeper dive into how to think about and reason through the diagnosis of medical presentations. The book is available in print, on your handheld device and in a fully searchable mode via the Access Medicine website available worldwide from McGraw Hill.
DR. CIFU: The music for this, the S2D podcast is courtesy of Dr. Maylyn Martinez. [upbeat outro music] [upbeat outro music] [upbeat outro music]