Seriously, we should stop to appreciate the effort Dr. Strong has invested to make such a great videos. I watched your videos as a 4th year medical student, I am watching them now as 5th year medical student and definitely I will watch them in my 6th year. They are informative, accurate, clinically relevant and FUN to watch! Thank you very much!
1. In type 1 RTA, there is reduced renal excretion of HCO3 (as measured by low fractional excretion of HCO3 in the urine). The serum HCO3 level is low because it is buffering the excess H+ ions that can't be excreted. 2. The hypercalciuria isn't caused by the RTA, but can be a cause of the RTA. The etiologies of hypercalciuria are numerous, and explained in more detail in my video on hypercalcemia. 3. It's normal gap because the chloride increases in proportion to the HCO3 decrease...
4, That's a really great question. I know it seems the opposite of what you would expect. I would guess that it's because type 2 RTA is usually caused by a relatively modest metabolic defect, whereas type 1 RTA is just more severe in terms of its effect on overall acid-base balance. I've never seen an evidence-based comparison of serum pHs in type 1 vs. type 2, but in my limited experience, type 1 RTAs seem to result in lower serum pHs than type 2. I don't know that for a fact though.
Possibly due to increased Na reabsorption & H+ excretion at the FUNCTIONING late DCT & collecting tubules under the influence of Aldosterone ! Remember that in type 2 RTA (Na/H+ antiporter) is NOT functioning in the PCT , as a result 65 % of Na reabsorption in the nephron will not take place & that excess of sodium filterate will be referred to the distal portions of the nephron for more exchange with K , H+ & NH4+ . That of course explains why in type 2 RTA we get variable urine pH , mild hypokalemia & low or even negative UAG ! LORD KNOWS BEST !
The videos are wonderful and I would like to point out in your approach to nagma you have mentioned UAG low or negative in type 2 RTA isn't it wrong sir?
In renal failure, how can you have a raised AG metabolic acidosis and a normal AG metabolic acidosis at the same time? What would the anion gap actually be for a patient who has both of these things at the same time?
Thanks for the great lecture. I got a question. What is the difference between RTA type 2 and GI loss? Is there any different lab or should I just depend on the history of the patient?
thank you very much for your effort the lecture is really informative. i've one question please. why our doctor in the UNI told us that in CRD espicially in the final stages the anion gap is elevated? you said that in RTA 2 there is an incresing in cl blood concentration as a compensation to low hco3 blood level , so my point is why that doesn't happen in ckd too , i mean the increse in cl concentration and hence normal gap anion in ckd? ... sorry about my bad english :)
In acute renal failure Cl- compensation is sufficient thus normal AG .on the other ,in CRD as the renal damage is much widespread , accumulation of organic acids occure(urea, phosphates,.....) and Cl- compensation would be insufficient thus AG is higher than in ARF. Hope this answers your question.
Thanks for the great video..but i am still confused with the normal anion gap acidosis..e.g in diarrhea the body losts hco3- so Ag=Na+K- (hco3+cl) and lost of hco3 should increase the anion gap..no?..oh I am so stupid....i dont understand this
Yes, the body loses HCO3-, but it also loses sodium in similar proportion, which helps to keep the anion gap normal. In addition, loss of sodium and volume activates the renin-angiotensin-aldosterone axis. As one consequence of the RAA axis, sodium reabsorption in the renal tubules is increased in an effort to restore volume; the mechanism by which this occurs can include coreabsorption with HCO3- (which limits the acidosis) or coreabsorption with Cl- (which keeps the anion gap from increaseing). The net result is a roughly 1:1 exchange of HCO3- and Cl- during diarrhea, in which the HCO3- is mildly reduced, and the Cl- is mildly elevated, with the overall anion gap remaining normal. Don't worry about being confused - the kidneys are confusing!
In type 1 RTA the dysfunction is in the k+\h+ counterport so there is a failure in the k+ uptake and in h+ excretion thus acidemia and hypokalemia ... In type 2 RTA the dysfunction is in the uptake of HCO3- thus leaving it in the urine which inhibits the absorption of Na+ cation in the PCT so more Na+ cations will reach the DCT where they are exchanged with k+ cations resulting in hypokalemia ....I hope this answers your question.
Sera Kim At the risk of upsetting renal physiologists and proponents of the Stewart approach to acid-base analysis, my quite serious recommendation for you is to ignore chloride when assessing acid-base status, with the exception of using it to calculate the anion gap. Some of the mechanisms for hyperchloremia in normal anion gap acidosis feel quite intuitive; for example, in diarrhea, in which the chloride content of stool is relatively low in comparison to water and other electrolytes - if a person is losing a lot of everything (include water) except chloride, naturally the chloride concentration will increase. Trying to reason through the hyperchloremia in RTA is not as intuitive, but luckily, not necessarily. If another viewer can think of a circumstance in which understanding the mechanism of hyperchloremia would be helpful, by all means, please post it here!
In type 4 RTA the defect is due to hypoaldosteronism or pseudohypoaldosteronism ! So the normal reabsorption of Na & excretion of K , H+ & NH4+ in the late DCT & collecting tubules doesn't take place ! So how comes the urine pH doesn't rise above the 5.3 point in type 4 RTA ?
Aldosterone works on reabsorption of Na+ and excretion of K+ (maybe a bit H+) of the principal cells lining the late DCT and collecting ducts. However the excretion of most H+ occurs in another special type of cells called Intercalated cell A which actively excrete most of H+ using ATP, and partly exchange H+ and K+. Its work is significant in acidosis, not by the trigger of Aldosterone. That's why RTA type 4/ hypoaldosteronism won't make urine pH lower.
Still , the reabsorption of K+ & excretion of H+ by the K+/H+ exchanger in the alpha intercalated cells takes place & that will result in net secretion 0f H+ in urine !You still can recall how a disease like Cushing syndrome (Adrenal insufficiency) is associated with acidosis due to impaired excretion of H+ in urine !Both principal cells & intercalated cells work as a SINGLE UNIT to promote Na reabsorption from urine & K , H+ , NH4+ excretion in urine .
Type 4 RTA Causes hyperkalemia , which results into reduce proximal tubule ammonia production ( by some unclear mechanisms ). So there is inadequate ammonia to buffer protons in the distal tubule resulting into acidic urine in these patients despite reduced H+ secretion. If buffer delivery to the distal nephron is increased, urine pH will rise despite persistent acidosis. [ Ref. : Harrison IM vol-2 16th edition, page- 1700 ]
Im sorry if this is a dumb question, but is normal anion gap metabolic acidosis synonymous with hyperchloremic metabolic acidosis? I.e. does hyperchloremia always occur in normal anion gap metabolic acidosis?
Adrian Bulfon Not a dumb question at all. Normal anion gap metabolic acidosis is not technically synonymous with hyperchloremic metabolic acidosis since it is possible to have the former without the latter (i.e. in the setting of concurrent hyponatremia). However, their list of etiologies is the same, and I think most people use the two terms interchangeably without causing any problems.
As far as I understand ; the process that determines the compensation of serum HCO3- with Cl in case of normal AG metabolic acidosis takes place in the alpha intercalated cells of the collecting tubules . At the level of the basolateral membrane of the alpha intercalated cells there is a membrane bound (anion exchange protein) called BAND 3 . That protein transports HCO3- extracellularly upgradiently to the blood in an electroneutral exchange for Cl that moves intracellularly downgradiently inside the alpha intercalated cell . In case of such metabolic acidosis ; the sharp drop of serum HCO3- levels results in impaired capacity of the BAND 3 to transport enough HCO3- ions to compensate for the reduced pH as well as increased influx of H+ intracellularly neutralizing the generated HCO3- by the CA II in the alpha intercalated cell . The net result will be inhibition of BAND 3 transporter & retention of Cl in blood . Hence the name : Hyperchloremic metabolic acidosis ! LORD KNOWS BEST !
Okay why am i not understanding how type 4 RTA causes low urine pH if Hydrogen is not being excreted? also why is type 2 giving an elevaated urine Ph if defect is Hc03 excretion?
Type 2 RTA has got a VARIABLE urine pH NOT an elevated one ! Possibly due to increased Na reabsorption & H excretion at the FUNCTIONING late DCT & collecting tubules under the influence of Aldosterone ! While your first question is an intelligent one that needs an answer from Dr.Strong !
Thanks for your quotation & clarification ! The textbook author mentioned that hyperkalemia interfered with ammonia production in the PCT ( by some unclear mechanisms ) resulting in impaired buffering of urine protons & subsequent lower urine pH ! So in that sense we should consider that NH4+ & protonated titrable acids such as SO4 - - & HPO4 - - don't contribute to the reduction of urine pH as free protons do .
Seriously, we should stop to appreciate the effort Dr. Strong has invested to make such a great videos.
I watched your videos as a 4th year medical student, I am watching them now as 5th year medical student and definitely I will watch them in my 6th year. They are informative, accurate, clinically relevant and FUN to watch! Thank you very much!
1. In type 1 RTA, there is reduced renal excretion of HCO3 (as measured by low fractional excretion of HCO3 in the urine). The serum HCO3 level is low because it is buffering the excess H+ ions that can't be excreted.
2. The hypercalciuria isn't caused by the RTA, but can be a cause of the RTA. The etiologies of hypercalciuria are numerous, and explained in more detail in my video on hypercalcemia.
3. It's normal gap because the chloride increases in proportion to the HCO3 decrease...
Thank you doctor for this lecture and to all your lectures. They are very interesting and full of information. It really helps me with my studies.
4, That's a really great question. I know it seems the opposite of what you would expect. I would guess that it's because type 2 RTA is usually caused by a relatively modest metabolic defect, whereas type 1 RTA is just more severe in terms of its effect on overall acid-base balance. I've never seen an evidence-based comparison of serum pHs in type 1 vs. type 2, but in my limited experience, type 1 RTAs seem to result in lower serum pHs than type 2. I don't know that for a fact though.
Possibly due to increased Na reabsorption & H+ excretion at the FUNCTIONING late DCT & collecting tubules under the influence of Aldosterone !
Remember that in type 2 RTA (Na/H+ antiporter) is NOT functioning in the PCT , as a result 65 % of Na reabsorption in the nephron will not take place & that excess of sodium filterate will be referred to the distal portions of the nephron for more exchange with K , H+ & NH4+ .
That of course explains why in type 2 RTA we get variable urine pH , mild hypokalemia & low or even negative UAG !
LORD KNOWS BEST !
Subscribed. Thanks for the detailed, yet succint, rundown of this pathophysiology. Looking forward to more of your content!
Thank you Doctor Eric Strong ! This could be a CBT for Insomnia , they r talking about. It is a good lecture.
The videos are wonderful and I would like to point out in your approach to nagma you have mentioned UAG low or negative in type 2 RTA
isn't it wrong sir?
why is there a hyperchloremia in normal gap acidosis but not in elevated gap metabolic acidosis? what's the mechanism of hyperchloremia?
Amazing video!!
In renal failure, how can you have a raised AG metabolic acidosis and a normal AG metabolic acidosis at the same time? What would the anion gap actually be for a patient who has both of these things at the same time?
tank u sr dis are very much useful ,sir i cant understand that how elevated gap metabolic acidosis and normal gap metabolic acidosis present together
Great video! Very well explained.
Thanks for the great lecture. I got a question.
What is the difference between RTA type 2 and GI loss?
Is there any different lab or should I just depend on the history of the patient?
thank you very much for your effort the lecture is really informative. i've one question please. why our doctor in the UNI told us that in CRD espicially in the final stages the anion gap is elevated? you said that in RTA 2 there is an incresing in cl blood concentration as a compensation to low hco3 blood level , so my point is why that doesn't happen in ckd too , i mean the increse in cl concentration and hence normal gap anion in ckd? ... sorry about my bad english :)
In acute renal failure Cl- compensation is sufficient thus normal AG .on the other ,in CRD as the renal damage is much widespread , accumulation of organic acids occure(urea, phosphates,.....) and Cl- compensation would be insufficient thus AG is higher than in ARF. Hope this answers your question.
Tarek Nayfeh Thank you very much . got it now :)
Thanks for the great video..but i am still confused with the normal anion gap acidosis..e.g in diarrhea the body losts hco3- so Ag=Na+K- (hco3+cl) and lost of hco3 should increase the anion gap..no?..oh I am so stupid....i dont understand this
Yes, the body loses HCO3-, but it also loses sodium in similar proportion, which helps to keep the anion gap normal. In addition, loss of sodium and volume activates the renin-angiotensin-aldosterone axis. As one consequence of the RAA axis, sodium reabsorption in the renal tubules is increased in an effort to restore volume; the mechanism by which this occurs can include coreabsorption with HCO3- (which limits the acidosis) or coreabsorption with Cl- (which keeps the anion gap from increaseing). The net result is a roughly 1:1 exchange of HCO3- and Cl- during diarrhea, in which the HCO3- is mildly reduced, and the Cl- is mildly elevated, with the overall anion gap remaining normal. Don't worry about being confused - the kidneys are confusing!
another question plz why there is hypokalemia in both rta 1 and 2 allthough there is acidosis which causes hyperkalemia as i know ?
In type 1 RTA the dysfunction is in the k+\h+ counterport so there is a failure in the k+ uptake and in h+ excretion thus acidemia and hypokalemia ...
In type 2 RTA the dysfunction is in the uptake of HCO3- thus leaving it in the urine which inhibits the absorption of Na+ cation in the PCT so more Na+ cations will reach the DCT where they are exchanged with k+ cations resulting in hypokalemia ....I hope this answers your question.
Tarek Nayfeh thank you again tarek
Tarek Nayfeh Thanks!
Can you please explain how the hyperchloremia occurs with a normal anion gap acidosis??
Sera Kim At the risk of upsetting renal physiologists and proponents of the Stewart approach to acid-base analysis, my quite serious recommendation for you is to ignore chloride when assessing acid-base status, with the exception of using it to calculate the anion gap. Some of the mechanisms for hyperchloremia in normal anion gap acidosis feel quite intuitive; for example, in diarrhea, in which the chloride content of stool is relatively low in comparison to water and other electrolytes - if a person is losing a lot of everything (include water) except chloride, naturally the chloride concentration will increase.
Trying to reason through the hyperchloremia in RTA is not as intuitive, but luckily, not necessarily. If another viewer can think of a circumstance in which understanding the mechanism of hyperchloremia would be helpful, by all means, please post it here!
very useuful videos! thankyou so much!
In type 4 RTA the defect is due to hypoaldosteronism or pseudohypoaldosteronism !
So the normal reabsorption of Na & excretion of K , H+ & NH4+ in the late DCT & collecting tubules doesn't take place !
So how comes the urine pH doesn't rise above the 5.3 point in type 4 RTA ?
Aldosterone works on reabsorption of Na+ and excretion of K+ (maybe a bit H+) of the principal cells lining the late DCT and collecting ducts.
However the excretion of most H+ occurs in another special type of cells called Intercalated cell A which actively excrete most of H+ using ATP, and partly exchange H+ and K+. Its work is significant in acidosis, not by the trigger of Aldosterone.
That's why RTA type 4/ hypoaldosteronism won't make urine pH lower.
Still , the reabsorption of K+ & excretion of H+ by the K+/H+ exchanger in the alpha intercalated cells takes place & that will result in net secretion 0f H+ in urine !You still can recall how a disease like Cushing syndrome (Adrenal insufficiency) is associated with acidosis due to impaired excretion of H+ in urine !Both principal cells & intercalated cells work as a SINGLE UNIT to promote Na reabsorption from urine & K , H+ , NH4+ excretion in urine .
Type 4 RTA Causes hyperkalemia , which results into reduce proximal tubule ammonia production ( by some unclear mechanisms ). So there is inadequate ammonia to buffer protons in the distal tubule resulting into acidic urine in these patients despite reduced H+ secretion. If buffer delivery to the distal nephron is increased, urine pH will rise despite persistent acidosis. [ Ref. : Harrison IM vol-2 16th edition, page- 1700 ]
Great video! thankyou so much!
Im sorry if this is a dumb question, but is normal anion gap metabolic acidosis synonymous with hyperchloremic metabolic acidosis? I.e. does hyperchloremia always occur in normal anion gap metabolic acidosis?
Adrian Bulfon Not a dumb question at all. Normal anion gap metabolic acidosis is not technically synonymous with hyperchloremic metabolic acidosis since it is possible to have the former without the latter (i.e. in the setting of concurrent hyponatremia). However, their list of etiologies is the same, and I think most people use the two terms interchangeably without causing any problems.
Eric's Medical Lectures Great, thanks a lot! Your video was extremely helpful as well!
As far as I understand ; the process that determines the compensation of serum HCO3- with Cl in case of normal AG metabolic acidosis takes place in the alpha intercalated cells of the collecting tubules .
At the level of the basolateral membrane of the alpha intercalated cells there is a membrane bound (anion exchange protein) called BAND 3 .
That protein transports HCO3- extracellularly upgradiently to the blood in an electroneutral exchange for Cl that moves intracellularly downgradiently inside the alpha intercalated cell .
In case of such metabolic acidosis ; the sharp drop of serum HCO3- levels results in impaired capacity of the BAND 3 to transport enough HCO3- ions to compensate for the reduced pH as well as increased influx of H+ intracellularly neutralizing the generated HCO3- by the CA II in the alpha intercalated cell .
The net result will be inhibition of BAND 3 transporter & retention of Cl in blood . Hence the name : Hyperchloremic metabolic acidosis !
LORD KNOWS BEST !
the physiologic base of urine gap should be explained in special lecture ?
An important question : Is urine an electroneutral fluid as blood in order to CREATE such UAG ?
Okay why am i not understanding how type 4 RTA causes low urine pH if Hydrogen is not being excreted? also why is type 2 giving an elevaated urine Ph if defect is Hc03 excretion?
Type 2 RTA has got a VARIABLE urine pH NOT an elevated one !
Possibly due to increased Na reabsorption & H excretion at the FUNCTIONING late DCT & collecting tubules under the influence of Aldosterone !
While your first question is an intelligent one that needs an answer from Dr.Strong !
Thanks for your quotation & clarification !
The textbook author mentioned that hyperkalemia interfered with ammonia production in the PCT ( by some unclear mechanisms ) resulting in impaired buffering of urine protons & subsequent lower urine pH !
So in that sense we should consider that NH4+ & protonated titrable acids such as SO4 - - & HPO4 - - don't contribute to the reduction of urine pH as free protons do .
Congrats ¡
Thanks
Yeah that’s