Normal Anion Gap Metabolic Acidosis (ABG Interpretation - Lesson 9)

[Applause] [Music] hello this is Eric strong and this is the ninth lecture in this series on understanding ABG's the topic today is normal anion gap metabolic acidosis the learning objectives are to know the differential diagnosis of a normal ni gap metabolic acidosis and to be able to identify the specific etiology of a normal anion gap in an individual patient overall I find the differential diagnosis of a normal ni gap metabolic acidosis is the most frustrating of the five major categories of acid-base disorders it feels just a little more random and less clinically relevant than the other categories which is really just a manifestation of the fact these problems on average are less acutely important than the pathologies that cause the other disorders it's also because the renal tubular acidosis in particular are complicated and completely understood and hard to remember but I will try to keep things as simple as possible as we will see again with the metabolic alkalosis there are two major ways to categorize the ideologies of a normal gap acidosis for the first way we consider whether the primary problem is located in the GI tract or the kidneys and whether that primary problem is a gain of hydrogen ions or a loss of bicarbonate although calling it a GI problem is a bit of a stretch hyper alimentation is frequently listed on this differential diagnosis this basically means that a person is being artificially fed either through tube beads or TPN at a rate far in excess of what his or her metabolism is able to process as a consequence of excessive protein loading there can be buildup of ammonium ion and other acids that exceed the capacity of the kidneys to handle specifically in the kidneys there are two types of renal tubular acidosis or RTA which along with renal failure results in a gain of hydrogen Merilee through the kidneys inability to excrete it normally I'll discuss the RTA is quite a bit in a few minutes hyperkalemia can also lead to a relative gain of hydrogen through two different mechanisms also discussed later on loss of bicarbonate in the GI tract is most commonly the result of diarrhoea but can also be due to surgical procedures such as external pancreatic drainage and ureteral diversion oral calcium chloride can be converted to calcium carbonate in the gut lumen providing a pathway for intestinal loss of bicarb cholestyramine is an anion exchange resin meant to exchange chloride with bile salts and thus aid in their elimination however bicarbonate can also bind to cholestyramine leading to a metabolic acidosis though this rare side effect is seen predominantly in patients with baseline renal insufficiency loss of bicarbonate in the kidneys is really only caused by type 2 renal tubular acidosis two additional ideologies of a normal anion gap acidosis that don't clearly fall into the above scheme are infusions of either normal saline or ammonium chloride the former effect is quite common and I'll talk about it a bit later on the other hand ammonium chloride is a rarely used medication indicated only for the treatment of metabolic alkalosis because a number of these conditions are uncommon or esoteric I actually prefer conceptualizing these ideologies according to this chart placing them into either common or uncommon causes of a clinically relevant acidosis and the common list are renal failure diarrhoea type for RTA and in fusion of saline in the uncommon list is everything else at this point as I did with the preceding lecture and as I will deal with the next several lectures I will discuss the more important of these ideologies in more detail one at a time I will also review a little of the pathophysiology of them along the way this will provide you the background needed to understand why these specific ideologies cause normal gap metabolic acidosis and why they present the way which they do the first group of ideologies to discuss is the renal tubular acidosis these are collection of disorders with the shared features of a normal anion gap metabolic acidosis a defect in the kidneys ability to maintain acid-base balance and the absence of overt renal failure here's a schematic of a nephron from the kidney that we saw in lecture 2 and we'll revisit again in lecture 10 the three major mechanisms of acid-base regulation in the nephron are shown and each is linked to one type of RTA type one RTA also known as distal RTA is caused by a defect in the collecting duct where hydrogen ions are normally excreted with simultaneous reabsorption of potassium type 2 RTA also known as proximal RTA is caused by a defect in the proximal convoluted tubule where bicarbonate is normally reabsorbed finally there is type 4 RTA which is not a kidney problem per se but rather a deficiency of the hormone aldosterone the ideologies of type 1 and 2 RTA can be broken down into those that present as children and those that present as adults when type 1 RTA presents in childhood the cause is usually one of a number of rare genetic disorders occasionally the RTA is idiopathic though many of these cases are likely genetic but we just haven't identified the gene or associated protein defect yet in adults ideologies include a variety of autoimmune disorders best described in Sjogren's syndrome rheumatoid arthritis and lupus as well as a number of drugs hypercalcemia obstructive uropathy cirrhosis and chronic toluene toxicity type 2 RTA and children is also usually due to various rare genetic disorders or as idiopathic in adults it may be due to multiple myeloma amyloidosis a variety of drugs or heavy metal toxicity this is a good place to point out that type 2 RTA can be further classified as either isolated which there is only a defect in the reabsorption of bicarbonate or it can be part of Fanconi syndrome in which a defect in the reabsorption of bicarb occurs concurrently with other defects of reabsorption in the proximal tubules specific molecules can include glucose phosphates and/or amino acids as a general rule any cause of isolated type 2 RTA can cause Fanconi syndrome with the exception of acetazolamide to understand the possible causes of type 4 RTA I'd like to review a little more of the physiology that controls the actions of aldosterone our review this is actually in slightly more detail in lecture 10 but on a basic level aldosterone regulation predominantly involves a cascade of hormones of pre hormones in the adrenal glands and the kidneys but also to some extent at the liver and lungs the Cascade begins in the liver where a pre hormone called angiotensinogen is produced angiotensinogen is converted into another pre hormone called angiotensin one with the help of the enzyme renin rena is produced in the juxtaglomerular cells in the kidney in response to low blood pressure or renal perfusion and requires locally produced prostaglandins angiotensin 1 travels in the systemic circulation to the lungs where it is transformed into angiotensin 2 by the angiotensin converting enzyme meanwhile in the adrenal glands various steroid precursors are converted into either the hormones cortisol or aldosterone and angiotensin 2 stimulates the synthesis of aldosterone specifically as you might recall both angiotensin ii and aldosterone effect acid based regulation in the kidney both hormones increased sodium reabsorption angiotensin 2 increases bicarb reabsorption and aldosterone increases both potassium and hydrogen secretion the net result as far as acid-base balance is concerned is a tendency towards metabolic alkalosis so anything that causes either low renin and/or low aldosterone levels can potentially lead to the opposite a metabolic acidosis specifically there are many medications which fear with Iranian angiotensin aldosterone axis first and most obviously are the anti hypertensive ACE inhibitors which as the name implies blocks the action of angiotensin converting enzyme angiotensin receptor blockers or ARB s have the same end effect NSAIDs interfere with two steps they block synthesis of the prostaglandins which mediate the production and/or release a treinen they also block the effect of angiotensin ii on aldosterone production heparin even as little as the doses used for DVT prophylaxis can interfere with the production of aldosterone by its direct toxic effects on the cells of the zona glomerulosa cyclosporine and bactrim both interfere with aldosterone effect on the distal tubules as does of course aldosterone receptor antagonists such as Perona lactone here is a list of the ideologies of type 4 RTA pathologies that specifically lead to low renin levels include mild to moderate renal insufficiency especially diabetic nephropathy NSAIDs acute glomerular nephritis a frothy pathologies that lead to low angiotensin ii levels only include ACE inhibitors in arabes finally a more direct problem just with low aldosterone can be due to adrenal insufficiency known as Addison's disease it can also be caused by medications has just discussed such as aldosterone antagonists heparin and cyclosporine and critical illness high circulating levels of ACTH may shunt steroid precursors towards the synthesis of cortisol and away from aldosterone patients with the 21 hydroxylase deficiency form of congenital adrenal hyperplasia also have low aldosterone levels as do a variety of other rare genetic disorders I'm going to briefly go over a comparison of the three RTA's so that you are able to distinguish them based on some common lab tests these cut-offs are going to be just general guidelines and not something to be particularly dogmatic about remember that the primary defect with type 1 is distal acidification with type 2 is reabsorption of bicarb in the proximal tubules and with type 4 it is hypoallergenic the serum by crops at the lowest levels are seen with type 1 and the highest with type for the serum potassium is normal or low with both types 1 and 2 but almost always elevated with type for your n pH is usually inappropriately high with type 1 is variable with type 2 and typically appropriately low with type 4 finally fractional excretion of bicarb which is an uncommon Lee ordered test unless one is attempting to specifically confirm a diagnosis of type 2 RTA is elevated in that circumstance but otherwise low I'm sure most of you have already wondered what about type 3 RTA I haven't actually mentioned that term yet the term type 3 RTA is inconsistently applied to a rare congenital deficiency of carbonic anhydrase to which results in features of both type 1 and type 2 RTA the vast majority of clinicians and certainly no one outside of pediatrics and genetics ever needs to worry about it another major cause of a normal ni gap acidosis is diarrhea intestinal secretions distal to the pylorus including those from the pancreatic duct are relatively alkaline as a consequence in normal gap acidosis frequently accompanies any condition resulting in excessive loss of these secretions this most commonly occurs with diarrhea but can also be seen with laxative abuse external pancreatic drainage Anantara cutaneous fistula and vomiting secondary to a distal small bowel obstruction in which the vomited bicarbonate from intestinal secretions can outweigh the vomited hydrogen ions and stomach acid in renal failure once creatinine clearance drops below approximately 40 milliliters per minutes ammonium excretion in the distal tubule begins to diminish as a consequence of retained hydrogen ions a normal ni gap acidosis develops the usually but not always accompanied by an elevated gap acidosis as a consequence of retained phosphate sulfate your eight and hip your eight all of which are unmeasured anions the normal anion gap component of the acidosis can be treated with either oral sodium bicarbonate or with a low protein diet as protein metabolism is the major source of ammonia infusions of normal saline particularly in patients who are volume replete can lead to a normal ni gap metabolic acidosis although there is very strong anecdotal evidence of this effect there is a relatively poor understanding as to the exact mechanism or its clinical significance which is thought to be relatively low the acidosis reverses very quickly once a lena stops provided the patient has normal renal function the retail diversions are a collection of surgical procedures predominantly used to redirect flow of urine after surgical removal of the bladder here is a picture of an ileal conduit in which a small segment of ileum is removed from the normal course of the GI tract the ureters are implanted into one end and the other end is sewn to the outer abdominal wall to form a stoma only urine and minimal intestinal secretions will flow out of the stoma which is known as a urostomy the mechanisms by which you read oral diversions can cause an acidosis are complex and varies slightly depending upon the specific procedure in question however this problem is most prominent when the ureters are implanted into the sigmoid colon this is known as a ureter rose sigmoid ostomy here is a simple schematic outlining the two major mechanisms by which metabolic acidosis occurs here first chloride in the urine enters the sigmoid colon where an anion exchange pump allows chloride to be removed from the sigmoid lumen in exchange for bicarbonate being pumped inside where it eventually is eliminated in the stool the second mechanism involves urea which encounters urea splitting bacteria normally present in the sigmoid these bacteria break urea down into ammonium ion which is then directly you are back through the gut wall using a process not yet entirely understood the net result is excretion of bicarb and reabsorption of hydrogen which results in the acidosis the final etiology I will talk about today is hyperkalemia there are two major mechanisms by which hyperkalemia can lead to a metabolic acidosis for the first let me show you a schematic of a cell where these yellow discs will represent potassium ions and the green ones will represent hydrogen in the presence of hyperkalemia there is a shift of potassium from the extracellular space to the intracellular space in exchange for a shift of hydrogen from the intracellular space to the extracellular space for the second mechanism here again as I diagram of the nephron you may remember from lecture 2 that hypokalemia is a stimulus in the collecting duct for potassium reabsorption simultaneous with hydrogen excretion in order to maintain electrical neutrality well the opposite also holds true in that hyperkalemia interferes with this process thus preventing hydrogen excretion from occurring normally this in essence can physiologically mimic a mild type 1 RTA for the final segment in this lecture I will talk a little bit about the urine anion gap which will then lead into a discussion of an approach to diagnosing the etiology of a normal anion gap metabolic acidosis the urine anion gap which I will subsequently abbreviated UAG is somewhat analogous to the serum anion gap discussed in detail in lecture 5 the calculation is slightly different however in this case it is the urine sodium plus a urine potassium minus the urine chloride so what exactly is this calculation telling us well here is a diagram of the normal breakdown of various positively charged cations and negatively charged anions in the urine as you can see the cations are composed predominantly of sodium and potassium the small contribution from some unmeasured cations which are predominantly ammonium well the anion our chloride with a slightly larger contribution from the unmeasured anions which are predominantly phosphates and sulfates your urine anion gap is essentially this difference here in most causes of been a balk acidosis here is what changes now in the kidneys effort to get rid of as much extra acid as possible there is a much greater amount of ammonium which significantly increases the amount of unmeasured cations in this situation the urine anion gap will be very low or in a specific case Illustrated here the urine anion gap may even be negative so in essence the urine anion gap is an indirect measure of the urine ammonium which cannot be easily measured directly once again in the normal case ammonium is low so the urine anion gap will be positive anywhere from positive 20 to positive 90 milli equivalents per liter in most forms of acidosis the ammonium will be high so the urine anion gap will be low or negative anywhere from negative 50 to positive 20 milliequivalents per liter metabolic acidosis that are not associated with a negative or near zero urine anion gap must be associated with impairment in the excretion of ammonium in the distal tubules this includes only chronic kidney disease and types 1 & 4 RTA so at this point let me present you one possible approach to determining the etiology of a normal ni gap metabolic acidosis this is not the only approach it's just the one that I personally find the most useful the first step is to either stop any infusion of normal saline or switch it to lactated ringers if this caused the acidosis to resolve then excessive saline infusion was the sole explanation if the acidosis persists then check if the creatinine clearance is less than 40 milliliters per minute if so then renal failure is the most likely explanation if creatinine clearance is greater than 40 then assess the serum potassium urine pH urine anion gap if the potassium is normal allow urine pH is low and your an anion gap is either low or negative then that GI cause is the explanation the specific ideology will almost always be evident from history at this point if the potassium is normal or low the urine pH relatively high and the urine anion gap high then type one RTA is the cause if potassium is normal or low and the urine anion gap is lower normal then type 2 RTA is the most likely cause this can be confirmed by measuring a fractional excretion of bicarbonate if the potassium is high your on pH low and your an anion gap high then inside for RTA is the explanation finally if the potassium is extremely high such as above 7 and urine pH low then hyperkalemia is the explanation in and of itself of course hyperkalemia has its completely separate differential diagnosis that I won't get into at this point in time so that concludes this lecture on the ideologies of a normal anion gap metabolic acidosis please continue on to lecture 10 which will discuss the ideologies of a metabolic alkalosis [Music] you [Music]

Channel: Strong Medicine

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Keywords: urine anion gap

Id: bBe2MU5r7fs

Length: 21min 34sec (1294 seconds)

Published: Fri May 11 2012