Renal Acid Base Flashcards
What makes up the larger volume of the kidney, medulla or cortex?
The cortex makes up 80%, and the proximal tubules make up around 90% of the cortical volume.
Describe the path of filtrate in the kidney
Afferent arteriole into glomerulus into the Bowman’s space into proximal tubule (S1 and S2 makes up the pars convoluta then S3 (pars recta)) then thin descending limb then loop of Henle then thin ascending limb then thick ascending limb then into DCT. About 10 DCT make up a single cortical collecting duct which then become a medullary collecting duct
What are the segments of the proximal tubules?
The pars convoluta: S1 - most reabsorption of primary urine S2 - organic anion/cation transporters Pars recta: S3 - Cl reabsorption, K secretion
Nearly everything is primarily absorbed in the prox tubule except for one element. Which is that?
Magnesium is primarily reabsorbed in Henle’s loop.
The percentage is as follows:
Proximal tubule reabsorption
- Water (67%)
- Na (65%)
- Cl (55%)
- HCO3 (90%)
- Urate (90%)
- Ca (60%)
- Mg (20-30%)
- Glucose (100%)
- Phosphate (100%)
- Amino acids (100%)
- Peptides/proteins(100%)
How does reabsorption work in the PCT?
Nearly everything is reliant on sodium transport. The Na/K ATPase on the basolateral membrane pushes 3 Na out for 2 K in. The K then passes out via a K-channel. This leaves a sodium gradient in the cell. The apical membrane then can utilise this Na gradient (low intracellular, high luminal Na) to excrete stuff. e.g. Na/H antiporter on the luminal membrane This also creates a sodium gradient that allows reabsorption of water. Approximately 20% of water is reabsorbed by AQP1 (aquaporin1) which is NOT regulated by ADH - it is CONSTITUENTLY expressed. The rest of water is resorbed via the intracellular tight junctions.
how is glucose resorbed after filtration in the glomerulus?
Recall that SGLT-1 inhibitors are a new class of diabetic medications.
What is the level of maximal bicarbonate resorption?
Bicarb is a bit like glucose… Once the level in the lumen exceeds a particular concentration, the body can’t resorb any extra.
In bicarb case, this occurs at 25. However in one of the RTAs (type 2) this occurs at around 15!
In the proximal tubule there are a bunch of ions that are secreted. How does this work?
There are anion pumps and cation pumps.
Because of this, anions compete amongst themselves to be excreted. Looking at the list below, if we give someone probenecid, it will compete with penicillin for secretion, leading to higher blood levels of penicillin! CLEVER!
The same occurs with cations.
How does the kidney deal with creatinine? What percent is filtered?
In a person with healthy kidneys, approx 90% is filtered and 10% is secreted. This means that creatinine level OVERESTIMATES our GFR by about 10%!
In a person with bad kidneys, the percent of secretion increases (this is because they don’t filter as much). In some patients this can be as much as 50%!
If you give a patient a drug that competes for the cation secretion pump, then you will cause a rise in creatinine. However, this doesn’t actually represent a worsening of renal function.
What makes the main components of acid excretion?
The body needs to excrete about 1 mmol/kg/day of non-volatile acid. In contrast, the lungs blow off about 215 times this!
The kidneys filter 65mmol/kg/day of bicarb!
They excrete about 1mmol/kg/day.
This represents about 13 plasma volumes worth of bicarb each day that is filtered at the kidney.
Because of this, we need to resorb all the bicarb - we’d never be able to ingest enough to keep up with requirement.
What is the renal handling of HCO3?
(where is there resorption and excretion?)
(see pic)
What is the mechanism for bicarb reabsorption?
The basolateral Na/K ATPase drives a sodium gradient. Then this gradient is used to anti-port Na/H. Then there is H in the lumen.
This H is combined with HCO3 by carbonic anhydrase. This then creates CO2, which freely transports across the luminal membrane.
Inside the PCT cell, the CO2 combines with water, then makes H2CO3. Intracellular carbonic anhydrase then creates H and HCO3.
The H is then re-secereted by the Na/H anti-porter that was mentioned earlier.
The bicarb and sodium are transported back into blood via Na/HCO3 symporter.
How can we diagnose type 2 RTA?
Well, one way is to give a patient bicarbonate and get the level to greater than 15, but less than 25 (the normal saturation level)
If a patient has bicarb in their urine with a serum level of 15-25, then it demonstrates a saturation of bicarb as seen with type 2 RTA (which can not resorb greater than 15.
If we have a metabolic alkalosis, how do we get rid of bicarb?
There is a luminal anion exchanger in the collecting duct. It is in the beta-intercalated cells. (note: beta-intercalated is important for excretion of bicarb)
How does the kidneys use ammonium to help renal handling of H+?
Interesting question.
A lot of the acid secreted by the Na/H anti-porter is actually in form NH4+. This is then able to create an interstital gradient, which then sets up a situation where the cortical collecting duct cell, “alpha-intercalated cell” can secrete more H+
explain how the kidneys utilise ammonia to secrete acid
it’s all in the picture
What do the principal cell of the collecting duct do? How does aldosterone control this?
Aldosterone is a steroid, and it binds to an intracellular receptor, but it promotes the process whereby Na is swapped for K.
Basically, the principal cell uses the Na/K ATPase to create an electrochemical gradient. This then leads to sodium travelling down its gradient to inside the cell at the loss of K.
Amiloride blocks this sodium passive diffusion channel seen on this picture.
What is the role of the alpha-intercalated cell?
It is a collecting duct cell that is important for the reabsorption of bicarbonate anion.
It utilised intracellular carbonic anhydrase to create bicarb and hydrogen within the cell. Then the bicarb uses chloride as a sym-porter to be resorbed.
Hydrogen is then secreted by a H-ATPase into the lumen. There is also a luminal H/K ATPase which resorbs potassium for loss of hydrogen
What is the role of the urinary anion gap?
How is it calculated?
The UAG is calculated Na + K - Cl.
It’s important to remember ammonia’s role in all this. It is a cation that is excreted, and chloride usually accompanies it.
If UAG > 0, there is a urinary acidification defect. This is because the sodium and potassium outweigh the chloride! If there were acidification (if the kidneys were excreting ammonia), it would cause the chloride to elevate. This is seen in type 1 RTA
If UAG < 0, urinary acidification is intact (there is more chloride than Na and K, suggesting there is an unmeasured cation). This is seen in diarrhoea or type 2 RTA
What investigations do we use to differentiate the renal tubular acidoses?
See the image, but it’s based around the critical differences.
Type 4 should have high potassium. It should have a urinary pH > 5.5
Type 2 will have acidic urine (pH < 5.5) and a negative UAG (urinary anion gap) because there is a lot of unmeasured ammonia (and consequently a lot of chloride) to make the gap negative.
Type 1 will have low NH4+ because acid secretion is the issue, and low K. These guys also get renal stones because the lack of distal acidification means they get low cysteine in CCD and follow on CaPO4 stones. In RACP terms, it is a NAGMA with hypoK and hyperCl with abdominal pain.
when approaching polyuria, how do you know if it’s increased water clearance, or if it’s increased solute excretion (leading to polyuria)?
A quick way is: Urinary osmol X daily urinary volume. If the daily urinary osmol clearance is greater than 1200-1500mOsm/day, then it’s solute excretion related.
Check out this sweet pic to help with differentials
How do we test for diabetes insipidus?
Have to do the water deprivation test and assess urinary/plasma osmolarity and response to fasting.
The test should be stopped if patient loses >5% weight or plasma osmol > 295.
If the patient has any renal response to fasting, their Uosm should climb. In renal DI, the Uosm usually stays super low. In central DI, it also stays low, BUT the addition of ADH causes the Uosm to increase by >50% post ADH.
In normal, we should get to >1000
How do we approach a hypokalaemia metabolic acidosis?
This is probably a high yield concept.
The first step is to differentiate the hypertensives from the normal BP.
If there is hypertension, then we check renin/aldosterone levels.
If there is no hypertension, then we check the urinary chloride.
Normotensive metabolic alkalosis –> check the urinary chloride. This is an important marker of volume.
If <20, it is not renal cause. If >20, renal cause
See image
This is a useful reinforcement of the concept.
Failure to reach normal urinary concentrations is not correct, because in polydipsia, they wash out their medullary gradient. This means that they can concentrate a bit, but not to normal levels. So, both partial central and polydipsia would fail to reach normal concentrations
In response to injected vasopressin, polydipsia should not have any response (or at least, less than 9%). Partial central and nephrogenic DI should have a partial response - at least 9 - 50%. Central DI would jump quite a lot (>50%)
How is water reabsorption managed in the CCD?
in this question we are speaking about water reabsorption.
See image
Answer: D
Acute hypovolaemia is mediated by prostaglandins.
Angiotensin II works on the EFFERENT arteriole
