L10 Acid/Base Phys II Flashcards
Respiration is regulated by plasma _______
Pco2
CO2 diffuses across the BBB, forms with water, and the dissociated H+ stimulates the chemo-sensitive areas of the medulla
Elevated Pco2 stimulates respiration and lowers the denominator in the Henderson/Hasselbach equations
The roles of the kidney in terms of acid/base physiology is to …
Stabilize plasma [HCO3-] at 22-26 mEq/L
Kidneys stabilize [HCO3-] by:
1) complete recovery of filtered bicarb when plasma [HCO3-] < 26mEq/L
2) synthesis of “new” HCO3- above and beyond that entering in the glomerular filtrate
3) excretion of HCO3- when present in excess (>26 mEq/L)
At plasma [HCO3-] > _______, HCO3- begins to appear in the urine.
> 26mEq/L
Reabsorption saturated at 40 mEq/L
The mechanism of HCO3- recovery in the kidneys is driven by:
H+ secretion
H+ formed in the ICF by reaction of CO2 and water is exchanged for Na+ in the proximal tubule or actively secreted in the distal tubule
HCO3- can then enter the peritubular capillary blood
HCO3- does not cross ….
The apical membrane
HCO3- is not reabsorbed itself. It’s all about the H+
______% of all filtered HCO3- is generally recovered
99.9%
85% by proximal tubule
10% by ascending thick limb of LOH
5% by collecting duct
Bicarbonate recovery in the proximal tubule - explain that shit…
The Na+/H+ exchanger on the apical membrane transports one Na+ into the cell and one H+ out. (2˚ active transport)
H+ binds to bicarb in the lumen, then H2CO3 splits into CO2 and H2O which diffuse back into the cell.
In the cell, they form H2CO3 again, then split into H+ and HCO3-. The bicarb binds to sodium and leases the cell through the Na+/HCO3- transporter on the basolateral membrane.
H+ is recycled to the Na+/H+ antiport to bring in more sodium.
Aldosterone also contributes to bicarbonate recovery by:
Stimulating the H+ ATPase, allowing for the transport of H+ from the tubule cell into the tubule fluid, where it can react with filtered HCO3- to form H2CO3, be transported back to HCO3- and pumped back into the ECF via the Na+/HCO3- transporter on the basolateral membrane
Characteristics of Renal compensation
1) One HCO3- is released into the peritubular capillaries for every HCO3- neutralized in the tubule
2) Once HCO3- is gone from the filtrate, luminal pH falls. May go as low as 4.4. Net H+ extrusion stops at this pH w/o additional buffering (pH gradient from 7.4 to 4.4 is ≈1000 fold)
3) Plasma acidosis promotes H+ secretion, and plasma alkalosis decreases H+ secretion
Metabolism liberates strong acids (ie sulfuric and phosphoric acid), and the HCO3- deficit is repaired by the kidneys which release more HCO3- into peritubular capillary blood than is present in filtrate.
Wait, WHAT?! HOW?
New HCO3- from tubule cell requires secretion of H+ in excess of filtered HCO3-. The tubular fluid pH can’t go below 4.4, so it uses phosphate and NH4+ to unload additional H+
When new bicarb is made in the distal nephron, it requires the secretion of H+ in excess of filtered HCO3-. How does the tubular fluid handle that excess H+, since it can’t go below pH 4.4?
The H+ combines with titratable acidity as a buffer
Titratable acidity? What the fuck is that?
Primarily filtered phosphate (some creatinine, lactate too)
pK for phosphate is 6.8 - excellent for buffering urine
H+ picked up by phosphate allows for the synthesis of additional HCO3-
H+ can also be excreted as NH4+.
Tell me about that one…
It’s a nifty process called diffusion trapping
Proximal tubule metabolizes glutamine from blood
Glutamine metabolized to yield NH3 and a-KG
• NH3 is highly diffusable and enters tubular fluid, is protonated in lumen to become NH4+
• a-KG is metabolized to HCO3-
Each glutamine yields two HCO3- (to the blood) and two NH4+ (lost in urine)
NH4+ is highly impermeable in most membranes of the nephron (esp the collecting duct)
Diffusion trapping describes the process by which…
H+ is secreted as NH4+
The synthesis of NH4+ from glutamine is regulated by …
Intracellular pH
Acidosis stimulates glutamine catabolism, allowing additional HCO3- to be returned to the blood to neutralize the H+
The primary mechanism for dealing with chronic acid loads (ie diabetic ketoacidosis)?
Synthesis of NH4+ from glutamine, as regulated by intracellular pH (in other words, diffusion trapping)
___________ also stimulates NH4+ synthesis, and __________ inhibits NH4+ synthesis
Hypokalemia stimulates and hyperkalemia inhibits
Remember those nifty H+/K+ exchangers across the cell membrane? Yeah, turns out they’re important.
Majority of fixed acid will be handled by…
NH4+, because titratable acid (primarily HPO4^2-) is limited
NH4+ synthesis is stimulated by acidosis (ie DKA, chronic renal failure)
Determining pH of blood from [HCO3-]?
EASY! Use the H/H equation!
pH = 6.1 + log [HCO3-]/(0.03 x Pco2)
For normal situations:
pH = 6.1 + log (24/(0.03 x 40)) = 7.40
Decreased bicarb OR increased Pco2 —> ACIDOSIS!
Increased bicarb or decreased Pco2 —> ALKALOSIS!
The three basic types of acid/base disturbances?
Uncompensated (“pure”) states: defect in HCO3- or CO2, no change in other parameter
Simple disturbances with compensation: defect in either HCO3- or CO2, with other parameter compensating (moving in same direction)
Mix states: BOTH HCO3- and CO2 are contributing to the acid/base disturbance, HCO3- and CO2 move in OPPOSITE directions
What does the mass action rule mean?
When Pco2 changes (either as primary problem or secondary compensation), it causes a small change in HCO3- due to mass action
So how do we estimate changes to [HCO3-] due to mass action?
Every 10 mmHg increase in Pco2 results in a 1 mEq/L increase in HCO3-, and every 10 mmHg decrease in CO2 results in a 2 mEq/L decrease in HCO3-
How do you go about classifying an acid-base disturbance?
1) determine whether the condition is normal, an acidosis, or an alkalosis (look at the plasma pH, dummy)
2) determine whether the condition has a respiratory or metabolic cause (is it PCO2, bicarb, or both?)
3) is there any compensation? Partial or complete?
Clinical conditions associated with metabolic acidosis
Acid ingestion, DKA, salicylate poisoning
