L10 Acid/Base Phys II

Question 1

Respiration is regulated by plasma _______

Answer 1

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

Question 2

The roles of the kidney in terms of acid/base physiology is to …

Answer 2

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)

Question 3

At plasma [HCO3-] > _______, HCO3- begins to appear in the urine.

Answer 3

> 26mEq/L

Reabsorption saturated at 40 mEq/L

Question 4

The mechanism of HCO3- recovery in the kidneys is driven by:

Answer 4

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

Question 5

HCO3- does not cross ….

Answer 5

The apical membrane

HCO3- is not reabsorbed itself. It’s all about the H+

Question 6

______% of all filtered HCO3- is generally recovered

Answer 6

99.9%

85% by proximal tubule
10% by ascending thick limb of LOH
5% by collecting duct

Question 7

Bicarbonate recovery in the proximal tubule - explain that shit…

Answer 7

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.

Question 8

Aldosterone also contributes to bicarbonate recovery by:

Answer 8

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

Question 9

Characteristics of Renal compensation

Answer 9

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

Question 10

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?

Answer 10

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+

Question 11

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?

Answer 11

The H+ combines with titratable acidity as a buffer

Question 12

Titratable acidity? What the fuck is that?

Answer 12

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-

Question 13

H+ can also be excreted as NH4+.

Tell me about that one…

Answer 13

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)

Question 14

Diffusion trapping describes the process by which…

Answer 14

H+ is secreted as NH4+

Question 15

The synthesis of NH4+ from glutamine is regulated by …

Answer 15

Intracellular pH

Acidosis stimulates glutamine catabolism, allowing additional HCO3- to be returned to the blood to neutralize the H+

Question 16

The primary mechanism for dealing with chronic acid loads (ie diabetic ketoacidosis)?

Answer 16

Synthesis of NH4+ from glutamine, as regulated by intracellular pH (in other words, diffusion trapping)

Question 17

___________ also stimulates NH4+ synthesis, and __________ inhibits NH4+ synthesis

Answer 17

Hypokalemia stimulates and hyperkalemia inhibits

Remember those nifty H+/K+ exchangers across the cell membrane? Yeah, turns out they’re important.

Question 18

Majority of fixed acid will be handled by…

Answer 18

NH4+, because titratable acid (primarily HPO4^2-) is limited

NH4+ synthesis is stimulated by acidosis (ie DKA, chronic renal failure)

Question 19

Determining pH of blood from [HCO3-]?

Answer 19

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!

Question 20

The three basic types of acid/base disturbances?

Answer 20

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

Question 21

What does the mass action rule mean?

Answer 21

When Pco2 changes (either as primary problem or secondary compensation), it causes a small change in HCO3- due to mass action

Question 22

So how do we estimate changes to [HCO3-] due to mass action?

Answer 22

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-

Question 23

How do you go about classifying an acid-base disturbance?

Answer 23

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?

Question 24

Clinical conditions associated with metabolic acidosis

Answer 24

Acid ingestion, DKA, salicylate poisoning

Question 25

Clinical conditions associated with metabolic alkalosis

Answer 25

Prolonged vomiting, antacid abuse, increased acid secretion/alkaline intake.

Question 26

Clinical conditions associated with respiratory acidosis

Answer 26

COPD, asthmatic attack, airway obstruction, chest wall dysfunction

Question 27

Clinical conditions associated with respiratory alkalosis

Answer 27

Stress-induced hyperventilation

Question 28

A primary acid load and a secondary respiratory alkalosis with pH below 7.35

Answer 28

Partly compensated metabolic acidosis

Question 29

A primary acid load and a secondary respiratory alkalosis with pH from 7.35 to 7.40

Answer 29

Completely compensated metabolic acidosis

Question 30

A primary base load and a secondary respiratory acidosis with pH above 7.45

Answer 30

Partly compensated metabolic alkalosis

Question 31

A primary base load and a secondary respiratory acidosis with pH from 7.4 to 7.45

Answer 31

Completely compensated metabolic alkalosis

Question 32

Complete respiratory compensation for metabolic A/B disturbances are…

Answer 32

Rare

In general, the lungs are only capable of partial compensation

Question 33

A primary respiratory acid load and a secondary renal increase in HCO3- with a pH < 7.35

Answer 33

Partly compensated respiratory acidosis

Question 34

A primary respiratory acid load and a secondary renal increase in HCO3- with pH between 7.35 and 7.4

Answer 34

Completely compensated respiratory acidosis

Question 35

A primary respiratory alkalosis with a secondary renal decrease in HCO3- with pH > 7.45

Answer 35

Partly compensated respiratory alkalosis

Question 36

A primary respiratory alkalosis with a secondary renal decrease in HCO3-, with pH between 7.4 and 7.45

Answer 36

Completely compensated respiratory alkalosis

Question 37

The kidneys are capable of __________ for chronic acid/base disturbances originating outside the renal system

Answer 37

Complete compensation

Unlike they lungs (those fuckers)

Question 38

Mixed acidosis is defined as

Answer 38

Metabolic acidosis + respiratory acidosis

Bicarb decreased while Pco2 increased

Low pH

Question 39

Mixed alkalosis is defined as

Answer 39

Metabolic alkalosis + respiratory alkalosis

Bicarb increased while Pco2 decreased

high pH