Diseases, Disorders information

Alport’s syndrome has glomerular lesions, hematuria and decreased GFR. Underline anterior lenticonus, cataracts, sensorineural deafness. First, lets look at prune-belly syndrome. Here is the prune-belly. Lacks abdominal musculature. Testes are not palpable. Renal abnormalities. Prune-belly syndrome. By the way, what do you notice? Is this a boy or a girl? Boy. Prune-belly syndromes are almost always in boys. And we can talk at some point about why that is, but it’s almost always in boys. Write it down. There are only about five reported cases in girls. And if they ask you that, tell them you want your money back. Prune-belly syndrome, boy, cryptorchidism, absence of abdominal musculature, renal problems. Hearing. Sensorineural high tone hearing loss. Cataract. This is the only condition, the only condition, that gives you anterior lenticonus. Everything else is posterior lenticonus in ophthalmology. This plus the characteristic glomerular lesion is Alport’s syndrome. I’ll go back and remind you, Alport’s syndrome; anterior lenticonus, cataracts, glomerular lesions, hematuria, decreased GFR.

Okay, we have a few more to go. This is a sort of characteristic … you see this little bulls-eye when you do your funduscopic? This is pretty characteristic. This is the lenticonus because what’s happening is you are looking in and the conical-shaped lens is like this, so you are going in and making your cuts in and I’ve never seen it described anywhere, but I’ve seen it a zillion times. And this is what it looks like. It almost looks circumferential. Bulls-eye in nature.

Tuberous sclerosis; you’ve heard about tuberous sclerosis. The renal abnormalities, renal angiomyolipoma, cystic kidneys and renal cell carcinoma. An important clinical link and association. Other features, underline adenoma sebaceae, underline CNS tubers, retinal phacoma and of course some of the skin, the shagreen patches, the White Mountain ash spots. We’ll talk about Drash syndrome, which is diffuse mesangial sclerosis, nephrotic syndrome in end-stage renal disease. The association here is Wilms tumor and male pseudohermaphroditism. So let’s first … looks like I have Drash syndrome up here first. Here’s mesangial sclerosis, diffuse mesangial sclerosis and ambiguous genitalia. If you get a patient, a case, with nephrotic syndrome and ambiguous genitalia like this, what study do you want to do? A renal ultrasound because you want to look for Wilms tumor. And that’s the link and association, a very important link and association here. This is named after Alan Drash, the first person. It’s also called Denny’s Drash syndrome, nephrotic syndrome in childhood, diffuse mesangial sclerosis, Wilms tumor, male pseudohermaphroditism. So these are males that have ambiguous genitalia. The females do not.

Finally, what is this? Recognizable? Anaphylactoid purpura, right. Remember, it is usually classically over the lower limbs and buttocks. It is alliterative, palpable purpura. Write down, as a link and association, palpable purpura. Because you can feel it. Little lumps. Palpable purpura on the lower extremities, crampy abdominal pain, arthralgia, peak at 4-5 years of age. It’s mediated by IgA immune complexes. Histology in the kidney, mesangial proliferation and/or epithelial crescents. The worse the biopsy the worse the prognosis. If you have nephrotic syndrome and nephritis, that is the worst outcome. We biopsy them and if we see crescents, that’s the issue.

I have included in your syllabus a list of syndromes that have renal disease in them and I’m going to highlight some of them here, not all of them, but highlight a few of them and show you some pictures. One or two of them you may see in the photo-quiz outside. I wonder how they got there? So we’ll just go through a few syndromes that will both help you clinically and might help you on the Boards.
A few words about medications. I recommend Cheap Canadian Pharmacy
Anti-Acidity Medications:
Canadian Pharmacy Nexium – NEXIUM works by decreasing the acid produced by acid pumps. NEXIUM deactivates some of the pumps to keep acid production under control. By reducing acid production in the stomach, NEXIUM reduces the amount of acid backing up into the esophagus and causing reflux symptoms.
Achipex – ACIPHEX is used for the treatment of persistent, frequent heartburn and other symptoms associated with acid reflux disease. Persistent and frequent occurrences are classified as 2 or more days a week.
Prevacid – Prevacid works by reducing the amount of acid produced in the stomach.
Syndrome number one, which I don’t have a picture of, is branchio-otorenal syndrome, BOR syndrome. You get dysplasia; unilateral renal agenesis is the renal anomalies, and other findings are branchial fistulas and in particular, preauricular pits and hearing losses. Those are underlined because those are the associations that you want to make. If you see somebody with a little pit in front of their ear and hearing loss, look for renal problems. Potter’s syndrome: renal failure, oligohydramnios. Remember that oligohydramnios tends to be associated with pulmonary hypoplasia. Because there’s not enough amniotic fluid to expand the lungs. You also get small posterior-set ears, micrognathia, beaked nose, wide set eyes. Here is a picture of Potter’s facies. These babies are usually stillborn. Micrognathia, look at the ears. Look how low set they are. This is what the kidneys look like; cystic dysplasia. Another picture of Potter’s facies. Ears are low set, not so low set, beaked nose, micrognathia. Pulmonary hypoplasia is the association.

Prune-belly syndrome; the renal abnormalities, dilated urinary tract, dysplastic, aplastic, multicystic and hydronephrotic kidneys. Underline absence of abdominal musculature, cryptorchidism. That’s called the triad because there are three of them. Cryptorchidism, absence of abdominal musculature, renal abnormalities. The triad.

How do you evaluate type II RTA? Again, hyperchloremia, metabolic acidosis. But the anion gap is negative. Remember I told you that for distal RTA the anion gap was positive. This one is not a problem with making ammonia. This is a problem just with leaking lots of bicarb. So the anion gap is negative. The urine pH is greater than 5.5 when the plasma bicarb is what is normal to you and me, but when the plasma bicarb falls below the threshold, the urine pH is low.

I am going to … this is another way to evaluate it. Again, this is something that pediatric nephrologists do. It’s a fractional excretion but instead of a fractional excretion of sodium, it’s a fractional excretion of bicarbonate. And we can do this, and this allows us to do that. Again, they will not be asking you that.

A quick word about type IV RTA. There is no type III. There was a mistake. Somebody made a mistake and so they called… we called just type IV. Type IV is so-called low-renin hypo-renin hypoaldosteronism. This again is a non-anion gap acidosis but it has hyperkalemia. Urine pH can look like type II RTA with a pH less than 5.5. Highly unlikely that they will ask you about this. Very unusual. It’s caused by true aldosterone deficiency, conditions which decrease renin secretion and conditions where the kidney cannot respond to mineralocorticoids. This is a reiteration; the diagnostic workup of suspected RTA. We look first for he serum anion gap. We see whether it is elevated. The metabolic acidosis is elevated. If it is you work up for a gap acidosis. If there is a normal gap, you want to evaluate for RTA. Then I put in how you go with RTA’s, either type II or type I and type IV. I’m going to skip over this, and I’m going to skip over metabolic alkalosis except to remind you that the laboratory studies for metabolic alkalosis will show you that besides a blood pH that is high, there is a low chloride, a low potassium, increased bicarbonate or CO2 in the blood. The few physical signs; tetany. Underline tetany and convulsions. This is one of the things that can give you tetany and convulsions, metabolic alkalosis.

The types; it is associated with many many things, and I’ve listed a number of them here. Genetically transmitted disease, autoimmune diseases and disorders associated with nephrocalcinosis. If you hear nephrocalcinosis and acidosis, think type I RTA, and there are a couple of situations here. Drugs that have tubular toxicity; we talked about hypokalemia with cisplatin and amphotericin. Amphotericin will also give you a situation of RTA. Amphotericin also gives you renal failure in very sick patients, but in patients that are not so sick and we are using lower doses of amphotericin, there is a tubular toxicity, and that’s amphotericin-B I’m talking about. Others include pyelonephritis obstruction and kidney transplant.

Type II RTA is different than type I RTA. It’s not that you can’t excrete hydrogen ions. It’s that the kidneys leak bicarbonate. There is a low threshold in the blood for spilling bicarbonate in the urine. Normally you and I start to spill about 22 … or kids, actually, start to spill 22-24. In type II RTA they start to spill at 15-16, so they begin to lose their bicarbonate with relatively low serum bicarbonates. The clinical findings, again, hyperchloremia. I can’t stress enough, hyperchloremia – metabolic acidosis. With what in the potassium? Low potassiums, low or normal. That’s the way to recognize this. High chlorides, low or low normal potassium with an acidosis. The urine pH is greater than 5.5 when the bicarbonates, or the serum bicarbonates or the CO2 is normal. But it can decrease to less than 5.5 when you get very acidotic. Because then you get underneath the threshold and the body is able to reabsorb all the bicarbonate, and in this situation the distal tubule is working fine. It’s only the proximal tubule that is messed up and spilling all the bicarbonate. The K can be low or normal. Never high. This is seen usually with Fanconi’s syndrome, but it may be isolated.
Renal tubular acidosis
So what is the Fanconi’s syndrome? The Fanconi’s syndrome is a disease of the proximal tubule, that has all of the listed criteria, or many of the listed criteria; proximal RTA, they have amino aciduria, glucosuria, phosphaturia and hypophosphatemia and hypokalemia. They have uricosuria. They spill uric acid and decreased plasma uric acid. They have rickets, growth retardation, polyuria, dehydration, and sometimes low molecular weight globulin proteinuria.
Metabolic alkalosis
What are examples? This is the one they will ask you. Number one, cystinosis. Most frequent cause. Galactosemia, Wilson’s disease are others. Glycogen storage disease, Wilson’s disease, galactosemia, but cystinosis, nephropathic cystinosis, is the archetypal one. Here are some other selected causes. The full group is in your syllabus; heavy metal poisoning, cisplatin, biphosphamide, and then some other nephrologic ones, and glue-sniffing. Now if you have an isolate, those with Fanconi’s syndrome, I’ve listed some causes of isolated proximal RTA that are shown here. It is highly unlikely they will ask you any of these. And they are listed here: sporadic, genetic, carbonic anhydrase inhibition.

How do we recognize renal tubular acidosis? Number one, what I said before; first have a blood pH. You’ve got to have acidosis. I can’t tell you how often I have been consulted by some of you out there who will remain anonymous, in the audience, who say, “Low CO2, low bicarbonate, we obviously have an acidosis. Please evaluate the acidosis for us.” And it turns out, of course, that it’s a compensation because the blood pH, when we got it, was 7.6. So number one, be sure you know the acid-base status. Start stepwise. Start with your first step which is; know the primary disorder. Then these patients are hyperchloremic. They have a normal anion gap. Not a high anion gap. They have a relatively low serum K for the degree of acidosis, and this is true of type I and type II RTA’s. And they have an inappropriately high urinary pH. If you have all of these, you more than likely have an RTA. So these are the characteristics. This right here is something to look at. If you don’t look at anything else in RTA, look at this. Because this is the link, this is the association that will allow you to get it through the test.

Now there are different types. We nephrologists have an incredible amount of imagination and wit, so we of course call them type I and type II, with our great creativity. Type I is called distal RTA. It is caused by a problem in the distal tubule with the inability to decrease the urine pH to 5.5 during acidosis. Because the kidney can’t push out hydrogen ions out of the body. There is one of a number of molecular defects that cause the kidney to be unable to kick out hydrogen ions. You eat 3 milliequivalents per kilo of hydrogen ion per day in your phosphates and your sulfates and the things that you eat. You can’t get rid of them in RTA. Thus, you become a big walking hydrogen ion. The associated problems with type I – this is an important association – nephrocalcinosis. Another; we’ve said before, hypokalemia and low urinary citrate. Remember the two types of acidosis that give you low potassium, DKA – because you are peeing out all that K – and RTA. RTA, relative hypokalemia. It turns out that you get a secondary hyperaldosteronism and that’s why you get hypokalemia. What’s important to remember is low acidosis, low K; low or normal K – even a normal-ish K – you’ve got to really think about it because the K should be high when you are very acidotic. Think DKA or RTA.

How do you evaluate these patients? They have a hyperchloremic metabolic acidosis and they have a positive urinary anion gap. That’s because these patients don’t make very much ammonia. The urine – a lot of the positives that are over here to balance out the chlorides, etc. – is ammonia and usually the sodium plus potassium minus chloride normally is a negative number. But in distal RTA the sodium plus the potassium minus the chloride is a positive number in distal RTA. We’ll get to proximal RTA in a minute. And in normals, it’s a negative number. The urine pH, for the sake of this discussion here, is always greater than 5.5. There are situations where it may be below that but not in a million years will they ask you. So for the situation that we are talking about here, with regard to 98% of RTA’s, urine pH always greater than 5.5. You can bicarbonate load these patients and do a study called a urine PCO2 minus blood PCO2 and the values are given here. This is a question for pediatric nephrology Boards. Not for general peds Boards. You won’t get asked it.

Metabolic alkalosis; you are alkalotic, you have a high CO2 with retained bicarbonate. The compensation is low ventilation. You decrease your ventilation and you drive up your PCO2. The respiratory alkalosis, the PCO2 is low as you are blowing PCO2 off. The pH is high, the bicarbonate excretion is your compensation, so your CO2 will be low. When you are studying, make sure you have a clear view of this before you go to this. So make sure you understand clearly what the primary problem is, and then look at the compensation and that will help you with your study. Do it in a stepwise fashion. Don’t even bother with the compensations until you are clear what the primary problem is. See the primary problem then look to the compensation.
Canadian pharmacy levitra
Okay, now, the next thing you do if you have an acidosis, and in particular is to determine the anion gap. The anion gap is the sodium minus the bicarbonate and chloride. Normally it’s 9-12. An increase in the anion gap over normal represents unmeasured anions and those are usually things like lactate, beta-hydroxybutyrate, that’s the so-called gap acidosis. Where you are dumping acids into the blood. A gap acidosis, those include lactic acidosis, uremia, diabetic ketoacidosis or organic acidemias. Other exogenous acids like salicylate or ethanol. Non-gap acidoses; most are either loss of diarrhea or other base from the body, usually from the GI tract but it can be from other places, or renal tubular acidosis. So gap acidoses are when you are dumping acids into the blood, a pathologic process is dumping acids into the blood. A non-gap acidosis is when you are losing something from somewhere that is usually basic. And that something from somewhere is usually diarrhea and bicarbonate, bicarbonate in the diarrhea.