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
Clinical conditions associated with metabolic alkalosis
Prolonged vomiting, antacid abuse, increased acid secretion/alkaline intake.
Clinical conditions associated with respiratory acidosis
COPD, asthmatic attack, airway obstruction, chest wall dysfunction
Clinical conditions associated with respiratory alkalosis
Stress-induced hyperventilation
A primary acid load and a secondary respiratory alkalosis with pH below 7.35
Partly compensated metabolic acidosis
A primary acid load and a secondary respiratory alkalosis with pH from 7.35 to 7.40
Completely compensated metabolic acidosis
A primary base load and a secondary respiratory acidosis with pH above 7.45
Partly compensated metabolic alkalosis
A primary base load and a secondary respiratory acidosis with pH from 7.4 to 7.45
Completely compensated metabolic alkalosis
Complete respiratory compensation for metabolic A/B disturbances are…
Rare
In general, the lungs are only capable of partial compensation
A primary respiratory acid load and a secondary renal increase in HCO3- with a pH < 7.35
Partly compensated respiratory acidosis
A primary respiratory acid load and a secondary renal increase in HCO3- with pH between 7.35 and 7.4
Completely compensated respiratory acidosis
A primary respiratory alkalosis with a secondary renal decrease in HCO3- with pH > 7.45
Partly compensated respiratory alkalosis
A primary respiratory alkalosis with a secondary renal decrease in HCO3-, with pH between 7.4 and 7.45
Completely compensated respiratory alkalosis
The kidneys are capable of __________ for chronic acid/base disturbances originating outside the renal system
Complete compensation
Unlike they lungs (those fuckers)
Mixed acidosis is defined as
Metabolic acidosis + respiratory acidosis
Bicarb decreased while Pco2 increased
Low pH
Mixed alkalosis is defined as
Metabolic alkalosis + respiratory alkalosis
Bicarb increased while Pco2 decreased
high pH
