Proton Handling and Renal Tubular Acidosis Flashcards
pH = 7.18 HCO3 = 9 pCO2 = 24 Anion gap = 12
constipation, Dry eyes and dry mouth. Pre existing diagnosis of Sjogrens syndrome. what is the acid base abnormaliy?
Low pH, low HCO3. metabolic acidosis.
look at compensation; bicarb in this case is down by 15. the appropriate comp is 1:1, so CO2 should be down by around 15. in this case, it is close to 25. there is no respiratory problem.
look at AG: AG normal. this is a normal ag met acid.
the prompt said she is constopated, so it’s not a GI loss. we must now differentiate between dig types of renal loss.
Normally, kidney reabsorb __ buffer, and excretes __.
Normally, kidney reabsorb bicarbonate buffer, and excretes hydrogen.
main site of bicarb reabsorption. How?
PCT.
from the lumen, sodium is exchanged for hydrogen going out, which is influenced by angiotensin II. throuhg the Na-H exchanger, H+ counters the bicarb that you want to reabsorb. in order to reabsorb bicarbinate, you need carbonic anhydrase enzyme – converts H+ and bicarb to CO2 and H2O. these go inside the cell. the CO2 and H2O convert back to H+ and HCO3, and the bicarb gets reabosrbed at the peritubular capillary with the sodium biarb synporter.
Proximal (type 2) RTA may be isolated or part of Fanconi’s syndrome.
___ ___ is the main site of H+ secretion. outline the premise of titratable acid excretion
distal nephron. `(collecting duct)
Titratable acidity is the amount of secreted H+ that is buffered by filtered weak acids is called titratable acidity. Phosphate as HPO42- is the main buffer in this system, but other urine buffers include uric acid and creatinine.
Hydrogen phosphate exists in two ways; when HPO4 or H2PO4. When the pH drops at the CCD because H+ is being pumped in by the H excretion pump, more H2PO4 exists. For every H+ we excite in the form of H2PO4, we have a bicarbonate
This is done via the kidney, which eliminates hydrogen in exchange for generating new bicarbonate as follows:
1) In the proximal tubule, hydrogen excretion is linked to sodium absorption. Carbonic anhydrase generates hydrogen and bicarbonate. The hydrogen is actively excreted into the renal tubular lumen, in exchange for sodium being absorbed, where it combines with filtered hydrogen phosphate, eliminating this acid. A luminal sodium/hydrogen antiporter controls this exchange (and is stimulated by angiotensin II). The generated bicarbonate is absorbed with sodium by a basolateral sodium/bicarbonate cotransporter (the energy for which is provided by the Na/K ATPase pump; angiotensin II also stimulates the basolateral sodium/bicarbonate cotransporter).
2) In the collecting tubules, bicarbonate is generated from carbonic anhydrase but hydrogen is actively secreted (not in exchange for sodium) by a hydrogen ATPase. The bicarbonate generated by carbonic anhydrase enters the interstitial fluid (then blood) in exchange for chloride, with a basolateral chloride/bicarbonate exchanger (the energy for this pump comes from a basolateral sodium/potassium pump, not shown). Aldosterone stimulates hydrogen excretion and bicarbonate resorption by stimulating the luminal hydrogen ATPase and the basolateral chloride/bicarbonate exchanger.
In this way, a new bicarbonate is generated (there is a net gain of bicarbonate!). The amount of filtered phosphate depends on the serum phosphate and glomerular filtration rate. In a normal animal, the amount of filtered phosphate is relatively constant. This method of generating bicarbonate (and excreting acid) is not how the kidney attempts to correct an acidemia or compensates for an alkalemia (this is done via renal ammoniagenesis).
Outline the ammonion chloride excretion process (happens in the CCD, but starts at the PCT)
theres an enzyme called glutaminase (PH dependent) at the PCT. when an acidosis occurs, glutaminase breaks down glutamine. glutamine produces ammonium, which takes place iof H+ on the Na+-H+ exchanger on the tubular lumen. it also creates alpha-ketoglutarate which creates more bicarb
NH4+ amonium (secreted into the tubular lumen) goes down the tubule where it is reaborbed idistally and broken down into NH3 AMMONIA and H+. H+ is secreted back into the lumen and can mop back up any bicarbonate that is excreted into the tubule.
at the cortical collecting duct, it secretes H+ and Cl- into the tubular lumen for excretion. if theform of acid is secreted in Hcl-, that would be painful. therefore, the ammonia existing in the tubule allows us to scoop up the H+ to form ammonium chloride.
The requirements for distal H+ secretion (in the form of ammonium chloride):
recall, that most stuff at the CCD happens on the __ __. there are cells around the PCs called _ _ cells which are important for distal H+ secretion. in the AICs, there has a _ _ ATPases that moves _+ into the _ _. When this proton pump in the AIC fails, we get rid of _ _+ (retain H+ and CL-), causing a __ __ _ acidosis.
when this AIC cell is to blame, we call this a type I _ _ _.
recall, that most stuff at the CCD happens on the principle cell. there are cells around the PCs called alpha intercalated cells which are important for distal H+ secretion. in the AICs, there has a proton pump ATPases that moves H+ into the tubular lumen. When this proton pump in the AIC fails, we get rid of LESS H+ (retain H+ and CL-), causing a normal anion gap acidosis.
when this AIC cell is to blame, we call this a type I renal tubular acidosis.
Recall the alpha intercalated cell at the cortical duct houses a proton pump atpase that secretes H+ into the lumen.
recall that if the principle cell reabosrbs sodium through ENAC without K+ leaving, it creates a NEGATIVE tubular charge. this is helpful for the secretion of H+ by the AIC.
there are two ways H+ secretion at the CCD can be impacted then:
- dysfunctional proton pump ATPase at the alpha intercalated cell
or 2. not creating a negative luminal charge.
How can you tell which cell at the CCD is to blame for the lack of H+ secretion?
if the principle cell is to blame, then it is hard to get rid of K+, so type IV RTK has normal anion gap metabolic acidosis and a HIGH POTASSIUM because we aren’t secreting as much K+
If the AIC cell is to plame, K+ pump on PC is fine, so the only thing that can make up the negative luminal charge is potassium. therefore, more potassium is pumped out and excreted. there is a high potassium excretion, but LOW K+ serum.
Type 4 RTA has __ K+ secretion
Type 1 RTA has ___ K+ secretion
Type 4 RTA has low K+ secretion
Type 1 RTA has high K+ secretion
if the principle cell is to blame, then it is hard to get rid of K+, so type IV RTK has normal anion gap metabolic acidosis and a HIGH POTASSIUM because we aren’t secreting as much K+
If the AIC cell is to plame, K+ pump on PC is fine, so the only thing that can make up the negative luminal charge is potassium. therefore, more potassium is pumped out and excreted. there is a high potassium excretion, but LOW K+ serum.
Distinguishing between the RTAs
Distal RTA (type I and 4) there is __ __+ production
Proximal RTA (Type 2) there is low __ wasting. the fractional excretion of __ would be under 15%
if ammonium chloride is reduced, something wrong distally. if ammonium production is normal or increased, there is probably a proximal tubular acidosis and you’d see bicarbonate wasting.
T/f you should measure ammonium directly
false. need indirect meaasure. urine net charge or urine osmolar gap
two ways of measuring NH4+.
- urine net charge
- urine osmolar gap.
- with metabolic acidosis, we should excrete 200 mmol/day of NH4+
major cations and anions that contribute to the urine net charge. Which ones are actually used in the calculation?
UNC: (Na and K) - Cl
how can urine net charge indicate NH4+ production in the kidneys?
negative urine net charge: NH4+ production is oK. if there is a lot of NH4+ (indicating that the production is okay, then there has to be a lot of Cl-, contributing to a more negative urine charge)
positive urine net charge: NH4+ production is impaired.
outline thought process when looking at this case.
she has constipation, dry mm. she has sjogrens disease.
this is a normal anion gap acidosis.
- calculate the urine net charge (Na+K) - Cl. this is a positive urine net charge. this is due to impaired distal nephron hydrogen secretion. Potassium is low serum K=2.3– ttkg is 13.3 so this is a principle cell issue secreting potassium.
she is hypokalemic. this is a type I RTA, where the problem lies in alpha I Cell hypokalemic acidosis.
She had sjogrens syndrome, so one of her targets in sjogrens is that A1C cells via t cell destruction/immunological damage. the ability to get rid of H+ is impaired since the atpase pump is destroyed.
