Acid-Base Balance Flashcards
List the rough percentages of reabsorption of the filtered load of HC03 throughout the PT, TAL, DT/CD, and out of nephron. What is take away message?
PT-80%
TAL-15%
DT/CD- 5%
output: 0%
The kidney wants to maintain and preserve the filtered load of HCO3-!
What are the main three roles of the kidney in terms of acid-base balance?
- reabsorb filtered load of HCO3
- Excrete non-volatile acids
- regenerate/replenish HCO3 that’s been consumed
What is a volatile acid?
One that breaks down into CO2
How much nonvolatile acid is excreted / day?
~140 mEq / Kg body weight / day
Net Acid Excretion Rate (NAE) equation
(UNH4V) + (UTAV) - (UHCO3*V)
TA= titratable acid = nonvolatile acid
Carbonic anhydrase is found in two regions of the proximal tubule. What is its function in both?
Inside cell: H2O + CO2 –> HCO3 + H+
(HCO3 gets reabsorbed, H+ gets secreted via the Na/H+ antiporter)
On luminal membrane: H+ + HC03 –> H2O + CO2
(CO2 diffuses down gradient and goes through cell membrane)
What are two major things that impact HCO3 reabsorption?
- Na reabsorption: if Na reabsorption increases, HCO3 reabsoprtion increases (due to Na/H antiporter, H gets secreted more, binds with HCO3, brings H2O and CO2 back into cell to make more HCO3 to get reabsorbed)
- CA inhibitors: blocks conversion of H2O + CO2 –> HCO3 + H+
Why do CA inhibitors make an effective diuretic?
- Enzyme cant convert H2O + CO2 –> HCO3 + H+
- less H+ gets secreted
- less Na gets reabsorbed (antiporter)
- diuretics block Na reabsorption
Outside of Acid/Base balance, what are 3 other regulators of HCO3 reabsorption?
- Filtered load of HCO3
- ECV (AII, SNS)
- K+ balance (if too much K+, gets put in cell, kicks out proton to maintain neutrality, intracellular pH increases)
What is the presence of CA in TAL, and how does it compare to in the PT?
CA is located only inside the cell, there is no CA in apical side. Reabsoprtion is thus limited since reaction doesn’t occur very quickly.
NB: H2O isn’t reabsorbed in the TAL!
Two main functions of Principal Cells in CD:
- reabsorb Na and H2O
2. secrete K+
Two types of intercalated cells in CD. Describe major differences/function
- alpha-IC - secrete acid via proton ATPase, H/K ATPase (both on apical side), and antiporter HCO3/Cl (on basal side, HCO3 getting reabsorbed)
- beta-IC - secrete base via antiporter HCO3/Cl (on apical side), and proton ATPase (on basal side, H+ getting reabsorbed).
Meat lovers make use of which intercalated cell the most?
Alpha-IC, since it secretes acid and there is a shit ton of acid in protein!
In addition to acid/base balance, what is another regulator of acid secretion?
For whatever reason, aldosterone stimulates alpha cells to secrete acid.
Titratable acids need to be excreted with associated proteins. Where does this buffering occurs in the nephron?
Collecting Duct
Which process is the most important aspect for acid base regulation?
Ammoniagenesis
Via what process is consumed HCO3 regenerated/replenished?
Ammoniagenesis
Breakdown of ____ turns into 2NH4 + 2HCO3. Where does this occur in the kidney?
glutamine, proximal tubule
If the kidneys done excrete NH4, what happens to it?
Gets picked up by liver, converted to urea + 2H+
NH4 is easily converted to NH3 + H+. Which form has a tough time crossing the membrane?
NH4+. Ammonia (NH3) is like COD, it can easily diffuse down its gradient
Trace the major steps of ammonium (NH4) through the nephron
- In the PT: H+ gets secreted (via Na/H antiporter) to join with NH3 in the lumen of the nephron
- gets kicked out of lumen in the TAL due to lumen’s (+) charge due to small K conductance in apical membrane
- NH4 –> NH3 + H+ in interstitial space
- NH3 gets reabsorbed in CD, and thus even greater driving force to convert NH4–>NH3 in interstitial space
- lots of H secretion of H+ in IC cells in CD (pH~4), traps ammonium
- NH4 excreted
Henderson–Hasselbalch equation
pH = 6.1 + log [HCO3]/ alpha*PCO2
where alpha = 0.03 (conversion factor mmHg–>mEq)
cut off pH for acidosis and alkalosis
acidosis
3 lines of defense (and time scale) to keep changes in pH at a minimum:
- ECF/ICF buffer–quick, seconds
- Respiratory compensation –> change in PCO2 –> change in pH – minutes to hours
- Renal Compensation/correction –> ammoniogenesis –hours to days
ECF/ICF buffers as a line of defense (3)
- Phosphates (everywhere)
- proteins (plasma, albumin)
- CO2/HCo3 (everywhere)
As ECF/ICF buffers, CO2/HCO3 is considered an “open” system while the other two are “closed.” What does this mean?
Open = can change [ ], vary equilibrium Closed = can't change concentrations, when there's an abnormality
metabolic acidosis and compensation
- due to decrease [HCO3]
- compensation = decrease PCO2
- increases net acid excretion
metabolic alkalosis and compensation
- due to increase [HCO3]
- compensation = increase PCO2 (increase pCO2 –> decrease pH –> more acidic)
- decrease net acid excretion
respiratory acidosis and compensation
- due increased PCO2 (which decreases pH= acidic)
- compensation = buffers
- increase net acid excretion
respiratory alkalosis and compensation
- due to decreased PCO2
- compensation = buffers
- decrease NAE
What are the two forms of metabolic acidosis?
- Anion gap type
2. Non Anion gap
What are causes of non-anion gap metabolic acidosis? (3)
GI losses (diarrhea), addition of mineral acid equivalents (HCl), renal tubular acidosis
anion gap “equation”
[Na+] - [Cl-] - [HCO3-]
What does a non-anion gap mean?
If add some acid H+A- to the system, the anion A- is used to measure the amount. If the anion of the acid is Cl-, then the decrease in HCO3 (to buffer the acid) will be matched by an increase in Cl, and the anion gap will be normal. However, if the anion of a nonvolatile acid is not Cl, then the anion gap will increase
normal level for anion gap
8-16 mEQ/L
Treat these 8 causes of acidosis differently than non-anion gap
Methanol Uremia (kidney failure) Ketoacids (diabetic-DKA, alcoholic, starvation) Paraldehyde INH toxicity Lactate Ethanol/ehylene glycol Salicyclate (from aspirin)
