Renal Regulation of Acid-Base Balance

Question 1

What is the effect and cause of rhabdomyolysis?

Answer 1

It is due to the release of myoglobin into the bloodstream

Question 2

In order to control pH what is secreted and what must be replenished?

Answer 2

H+ will be secreted and the kidneys must prevent the loss of HCO3- in the urine as it is used to neutralize much of the acid.

Question 3

What is the pH of urine around?

Answer 3

It is usually low due to the secretion of H+ so therefore it is acidic

Question 4

How do the kidneys secrete a large amount of H+ if they can only secrete urine with a pH of 4.0 - 4.5?

Answer 4

They must excrete H+ alongside buffers like Pi

Question 5

What term is used to refer to the urinary buffers?

Answer 5

Titratable Acids

Question 6

Besides the excretion of H+ as a titratable acid what other mechanisms contribute to the maintenance of the acid-base balance?

Answer 6

It is done through the synthesis and excretion of ammonium (NH4+)

Question 7

Where does most of the HCO3- reabsorption occur?

Answer 7

In the proximal tubule (80%)

Question 8

What is the predominant buffer in the proximal tubule?

Answer 8

HCO3- because the CO2 hydration reaction predominates due to presence of carbonic anhydrase in the border.

Question 9

What is the level of net H+ secretion in the proximal tubule?

Answer 9

Net H+ secretion of H+ is low due to the neutralization of H+ with HCO3- during HCO3- ion reabsorption

Question 10

What are the main buffers in the distal tubule and the collecting duct?

Answer 10

Phosphate and ammonium ions dominate due to the scarcity of carbonic anhydrase

Question 11

What is the net secretion of H+ in the distal tubule and the collecting duct?

Answer 11

It is very high due to strong proton pumping and buffering with Pi and NH4+

Question 12

What is Type I-Renal Tubular Acidosis?

Answer 12

It is distal tubule RTA and is the failure of the distal nephron to secrete H+ which leads to increased back-leaking of H+ and may be caused by H+ pump failure.

Question 13

What is Type II-Renal Tubular Acidosis?

Answer 13

It is proximal tubule RTA and is the failure of the proximal nephron to recycle H+ due to low carbonic anhydrase and decreased HCO3- reabsorption.

Question 14

What is the [HCO3-] that HCO3- is regulated at?

Answer 14

It is regulated at a concentration near the renal plasma threshold

Question 15

What processing of HCO3- occurs in the PT?

Answer 15

80% reabsorption

Question 16

What processing of HCO3- occurs in the DT and CD?

Answer 16

20% reabsorption

Question 17

How does the GFR regulate HCO3- reabsorption?

Answer 17

Reabsorption rate of the HCO3- is matched to changes in the filtered load via GT balance

Question 18

How does the systemic acid-base balance regulate HCO3- reabsorption?

Answer 18

Respiratory acidosis and increase in arterial PCO2 or metabolic acidosis and decreased [HCO3-] will lead to the acidification of the ICF.

This causes the insertion of the apical H+-ATPase that leads to increased H+ secretion and decreased HCO3- reabsorption.

Question 19

How does aldosterone regulate HCO3- reabsorption?

Answer 19

Increased aldosterone will lead to increased H+ secretion in the intercalated cells of CD.

Increased aldosterone will increase Na+ reabsorption and lead to increased H+ secretion.

Question 20

How does arterial [K+] regulate HCO3- reabsorption?

Answer 20

Increased K will increase K+-H+ exchange and lead to extracellular acidosis -> hyperkalemic metabolic acidosis

Decreased K will lead to hypokalemic metabolic alkalosis.

Question 21

How does the arterial [Cl-] regulate HCO3- reabsorption?

Answer 21

Increased [Cl-] will decrease HCO3- reabsorption and decreased will cause the opposite

Question 22

How does the extracellular fluid volume regulate HCO3- reabsorption?

Answer 22

During expansion of ECF, HCO3- reabsorption will be inhibited to to dilution of plasma [HCO3-]

Question 23

How does the Na+ balance regulate the HCO3- reabsorption?

Answer 23

Retaining Na+ will decrease HCO3- reabsorption and losing Na+ will increase HCO3- reabsorption

Question 24

What is the minimal urinary pH around and how does it reach such impressively low levels?

Answer 24

It is around a pH of 4.4 and it demonstrates the ability of the distal nephron to secrete H+ against a strong acid gradient.

Question 25

What are sources of free H+ in the urine?

Answer 25

Fixed acids - H2SO4

Titratable acids - H3PO4

Question 26

What acid is not a source of free H+ in the urine?

Answer 26

Carbonic acid

Question 27

What is the role of HPO4(2-) as a titratable acid?

Answer 27

It can combine with secreted H+ ions and make H2PO4- and the negatively charged anion is lipid insoluble so there is no back diffusion.

Question 28

What is the role of diffusion trapped ions and how do they “trap?”

Answer 28

NH3 reacts with secreted H+ to form NH4+ and NH4+ is charged and lipid impermeable, which traps the H+. NH3 is made from deamination reactions and it is freely permeable across tubular cells.

Question 29

What happens to NH4+ in chronic acidosis?

Answer 29

NH3 production increased in acidosis which allows for increased H+ secretion as an adaptation to the acidosis

Question 30

How is HCO3- and H+ balanced through NH4+?

Answer 30

For each secreted molecule of NH4+ a new molecule of HCO3- is added to the ECF