Kidney Lecture 3:Urine pH and Drug Removal

Question 1

Possible routes for substances entering nephron

Answer 1

Substance X
Partially Filtered
Mostly Secreted
Fully Excreted

Substance Y
Partially Filtered
Partially Reabsorbed
Partially Excreted

Substance Z
Partially Filtered
Fully Reabsorbed
Not Excreted

Renal processing of a substance based on several factors
To what degree the substance is filtered?
How much is reabsorbed?
How much is secreted?
What factors alter the amount filtered, reabsorbed, or secreted?
amount excreted= amount filtered+ amount secreted - amount reabsorbed

Question 2

A note on proteins

Answer 2

Whole proteins and protein-based drugs are not excreted by kidneys

Exception in cases of diminished kidney function

Proteinuria : high levels of protein in urine

Question 3

Possible routes for substances entering kidney

Answer 3

Balance of filtration, secretion, and reabsorption

Question 4

Describe how kidney regulates blood and urine pH

Answer 4

Acidosis and alkalosis
Regulation of carbonate
Reabsorption of filtered carbonate
Generation of new carbonate via loss of H+ bound to phosphate
Generation of new carbonate via glutamine metabolism

Question 5

Role of urine pH in drug excretion

Answer 5

Acidic vs Alkaline urine and drug ionisation

Question 6

Regulation of body pH

Answer 6

Carbonic Anhydrase - Key enzyme in acid-base homeostasis

Adding or subtracting carbonate (HCO3-) lowers or raises H+ by influencing this equation

Kidney regulates HCO3- and thereby pH

Question 7

Carbonate Reabsorption

Answer 7

Carbonic acid created in tubular cells breaks down into H+ and HCO3-
H+ transported into tubules, combines with filtered HCO3-

HCO3- transported into body

While filtered HCO3- disappears, HCO3- generated inside cell enters the body

Net result : no loss of HCO3-

Question 8

Carbonate Generation – H+ Secretion

Answer 8

Carbonic acid generated in tubular cells

H+ combines with filtered phosphate (HPO42-) and is excreted

HCO3- transported into body

Net result: Gain of HCO3-

Question 9

Carbonate Generation – Glutamine Meabolism

Answer 9

The amino acid glutamine enters tubule cells either from the filtrate or blood plasma

Glutamine is metabolised inside the cell to ammonia (NH4+) and HCO3-

Ammonia secreted into the tubules and excreted

HCO3- transported into the body

Net result: Gain of HCO3-

Question 10

Body pH has to be tightly balanced as many process are dependent on pH

Answer 10

When the body loses hydrogen ions (H+), pH increases becoming more alkali – Akalosis

Response to alkalosis

H+ secretion into tubules cannot keep up with filtered HCO3-
Excess HCO3- excreted

Glutamine metabolism decreased reducing HCO3- generation

When the body gains hydrogen ions (H+), pH decreases becoming more acidic – Acidosis

Response to acidosis

Lots of H+ is secreted into tubules
All filtered HCO3- is reabsorbed
Additional HCO3- is absorbed as H+ excreted bound to phosphate

Glutamine metabolism enhanced generating more HCO3-

Question 11

Urine pH and drug excretion

Answer 11

Most drugs are either weak acids or bases

In alkaline urine, acidic drugs are ionised

In acidic urine, alkaline drugs are ionised

Ionised drugs are more water soluble, which increases their excretion