acid base

Question 1

According to the Henderson Hasselbach equation, raising __ or lowering __ would increase pH.

Answer 1

Raising HCO₃^- or lowering pCO₂

Question 2

Answer 2

Uncompensated metabolic acidosis = Moving down along a pCO2 diagonal to a lower bicarbonate

Uncompensated respiratory acidosis = Moving from one pCO₂ diagonal to a higher pCO₂ diagonal

Question 3

What are the two types of acid loads?

Answer 3

CO₂ = respiratory acidosis

Nonvolatile acids = metabolic acidosis

Question 4

Causes of metabolic acidosis (nonvolatile acids)

Answer 4

• Exogenous acid loads
  
  • Salicylate, methanol, ethylene glycol
• Excess endogenous acid production
  
  • Ketoacids, lactic acid
• Decreased renal excretion of normal endogenous acids
  
  • Renal failure
• Loss of alkali
  
  • GI losses (e.g. diarrhea), urine losses (e.g. proximal tubular acidosis)

Question 5

Alkali loads

Answer 5

• Excess CO₂ removal = respiratory alkalosis
• Nonvolataile alkali = metabolic alkalosis
  
  • Exogenous alkali
    
    • NaHCO₃ administration
  • Loss of acid
    
    • GI losses (e.g. gastric fluid)
    • Excess urine H+ losses

Question 6

A small increase in pCO₂ will immediately cause

Answer 6

an immediate change in the cerebral interstitial pH that will activate chemoreceptors –> hyperventilation to blow off CO2

Question 7

Increase in nonvolatile acids or a decrease in [HCO₃^-] will cause..

Answer 7

a slower ventilatory response because it takes longer for nonvolatile acids and HCO₃- to cross the BBB to reach central chemoreceptors

Question 8

The ventilatory response to metabolic acid-base disturbances is not achieved for ___

Answer 8

12-24 hours!

Question 9

Does urine have bicarbonate in it?

Answer 9

Nope.

70-80% of filtered bicarb is reabsorbed at the proximal tubule

The rest is reabsorbed at teh more distal segments

Question 10

What are the 2 ways kidneys regulate HCO₃- concentration?

Answer 10

• Reabsorption of HCO₃^-
• Generation of new HCO₃^-

Question 11

How does the kidney produce additional HCO₃^- beyond what was filtered at the glomerulus?

Answer 11

It excretes acid (titratable acid and ammonium), generating bicarb in the process.

Net acid excretion = Amt of bicarb regeneration

Question 12

The kidney excretes titratable acid and ammonium to regenerate bicarb.

What is titratable acid?

Answer 12

Protons coupled to urinary buffers like phosphate

The nephron can’t excrete free protons that well.

Question 13

Under normal conditions, the amt of titratable acid excreted is ____ at the amt of ammonium excreted.

Under acidic conditions, which one gets excreted more?

Answer 13

Normal: it’s about half&half

Acidic: Way more NH₄⁺ is excreted

Question 14

What is the equation of net acid excretion in the urine?

Answer 14

Net acid excretion =

titratable acid + ammonium - urinary bicarbonate

Question 15

Recall how HCO₃^- is reabsorbed at the proximal tubule

Answer 15

• Na,H exchanger on the apical membrane sends out H+ into the lumen, which combines with HCO₃^- to form H₂CO₃
• Carbonic anhydrase turns it into CO₂ + H₂O
• CO₂ enters the proximal tubule cell, where another carbonic anhydrase combines it with OH- to reform HCO₃^-​
• An Na,HCO₃^-​ exchanger on the basolateral side sends both Na+ and HCO₃^-​ out into the blood.

Question 16

What drives the Na,H exchanger on the apical side?

Answer 16

The basolateral Na,K+ ATPase keeps [Na+] in the cell low –> driving force to take in Na+ and send out H+

Question 17

How is proximal tubule bicarbonate reabsorption regulated?

Answer 17

pH

peritubular bicarbonate

extracellular volume status

hormones

Question 18

pH & bicarbonate reabsorption

Answer 18

Factors that decrease intracellular pH increase the amt of H+ available for secretion –> allosterically enhance the Na,H-exchanger to promote reabsorption.

• Ex) Increased pCO2 will decrease pH
• Ex) Chronic K+ depletion will decrease pH
• Chronic acidosis may also increase the # of apical Na,H-exchangers and basolateral Na,HCO₃^- transporters in the proximal tubule.

Question 19

Peritubular bicarbonate & HCO₃^- reabsorption

Answer 19

Decreased peritubular HCO₃^- will increase reabsorption

Question 20

Extracellular volume status & proximal bicarbonate reabsorption

Answer 20

Increased ECFV will inhibit HCO₃- reabsorption

Decreased ECFV will promote reabsorption

(just think starling forces)

Question 21

Hormones that influence HCO₃^- reabsorption:

Adrenergic agonists

Angiotensin II

Parathyroid hormone

Glucocorticoids

Answer 21

Adrenergic agonists & Angiotensin II activate the apical Na/H exchanger. (Maintains metabolic alkalosis during volume or Cl- depletion)

Parathyroid hormone decreases reabsorption (though hypercalcemia increases it)

Glucocorticoids are involved in chronic adaptation to acidosis through the Na/H exchanger.

Question 22

While the distal tubule isn’t as good at secretingH+ and reabsorbing HCO₃^- as the proximal tubule, it can generate a large transepithelial pH gradient because of its ____.

This is used to drive HCO₃^- reabsorption

Answer 22

H+ ATPase & H,K-ATPase both secrete H+ to drive HCO₃^- reabsorption

Question 23

How does H+ secretion cause HCO3- generation in an intercalated cell of the collecting tubule?

Answer 23

• H+ secretion via H+ ATPase and H-K ATPase lowers intracellular [H+]
  
  • These H+ will combine with an ion like phosphate to form a tiratable acid in the urine like H₂PO₄-
• This drives the carbonic anhydrase reaction to keep splitting up H₂CO₃ into H+ and new HCO₃-
• New HCO₃- gets reabsorbed via the HCO₃-/Cl exchanger

Question 25

Bicarbonate secretion would only occur if you have

Answer 25

metabolic alkalosis

Question 26

What stimulates H+ secretion at the collecting tubule?

Answer 26

* Increased **Na+ reabsorption** --\> negative lumen voltage drives H+ ATPase to secrete more H+ into the lumen * Increased **mineralocorticoids** * **K+ depletion**

Question 27

Why is there a minimal urine pH achievable in urine?

Answer 27

The elctrogenic H+ATPase is sensitive to luminal pH - the amt of H+ it can excrete as titratable acid depends on how much urinary buffer is available.

Question 28

Most ammonia at physiologicla pH exists as

Answer 28

NH₄⁺

Question 29

Metabolism of ____ forms one HCO₃- for every NH₄+ excreted

Answer 29

glutamine

Question 30

Which part of the kidney is responsible for most ammonia production?

Answer 30

proximal tubule

Question 31

What factors alter ammonia production?

Answer 31

* **Acidosis** increases NH3 production * **Hyperkalemia** suppresses NH3 production * **Hormones**

Question 32

Pathway of ammonia in the nephron

Answer 32

1. **Produced in the proximal tubule** 1. **Glutaminase** breaks glutamine into NH₄⁺ 2. **Na,H****-exchanger** drives NH₄⁺'s breakdown into H and NH_3, which will diffuse into the lumen 2. **Reabsorbed at the thick ascending limb** 1. **Na-K-2Cl cotransporter** sometimes uses NH4+ insead of K+ 3. **Secreted via diffusion at the collecting tubule****​**

Question 33

Lactic acid and keotacid production are decreased by

Answer 33

a low pH

Question 34

How do the kidneys respond to metabolic acidosis?

Answer 34

Lowered HCO₃- in the plasma means less is getting filtered -\> kidney increases **bicarbonate reabsorption & generation** Low pH, glucorticoids, mineral corticoids, distal delivery of non-reabsorbable anions --\> **H+ secretion into the urine**

Question 35

What might *prevent* HCO₃^- excretion in metabolic alkalosis?

Answer 35

ECFV depletion will * decrease GFR * Increase prox tubule bicarb reabsorption * Release angiotensin & mineralcorticoids * Mineral corticoids stimulate H+ secretion * Cl- depletion * K+ depletion -\> stimulates H+ secretion