Mechanisms of acid-base balance

Question 1

What is the normal extracellular concentration of H+?

Answer 1

40 nmol/L

Question 2

What is the normal plasma pH range?

Answer 2

7.35-7.45

Question 3

Outside what range of plasma pH is considered incompatible with life?

Answer 3

6.8-7.8

Question 4

What is the urine pH range?

Answer 4

4 - 8.5

Question 5

What controls the PCO2?

Answer 5

Alveolar ventilation

Question 6

What controls plasma HCO3- concentration?

Answer 6

Renal excretion of H+ and reabsorption of HCO3-

Question 7

What are the two main buffers: intracellular and extracellular?

Answer 7

Intracellular: H2PO4- —–> H+ + HPO42-
Extracellular: H2CO3 —–> H+ + HCO3-

Question 8

Describe where most of the buffering takes place in the four kinds of acid-base imbalance.

Answer 8

Metabolic Acidosis - 80-85% intracellular
Metabolic Alkalosis - 30-35% intracellular
Respiratory Acidosis + Alkalosis - almost ALL intracellular

Question 9

What are the four sources of H+ ions in the body?

Answer 9

Physiological - carbohydrate and fat metabolism, sulfur containing amino acids
Pathological - hypoxia —-> anaerobic respiration —-> lactic acid
Or diabetes —–> ketoacids

Volatile acids - from carbohydrate and fat metabolism (results in CO2 production - CO2 is lost through respiration)
Non-Volatile acids - from protein metabolism (these H+ are excreted by the kidneys)

Question 10

In which three regions of the nephron does renal H+ excretion take place?

Answer 10

Proximal convoluted tubule
Thick ascending limb of the loop of Henle
Outer medullary collecting duct

Question 11

What transporters are involved in the renal excretion of H+ in the proximal convoluted tubule and in the collecting duct?

Answer 11

PCT
Na+/H+ exchanger : H+ secreted into lumen

HCO3-/Na+ cotransporters (basolateral membrane): bicarbonate ions are returned to systemic circulation

Collecting Duct
H+ ATPase
Cl-/HCO3- exchanger (basolateral membrane)

Question 12

Describe the process of excretion of H+ and retention of HCO3-.

Answer 12

H+ goes out of the cell via a Na+/H+ exchanger
H+ reacts with HCO3- in the filtrate to form H2CO3
Carbonic anhydrase converts H2CO3 to H2O + CO2
H2O + CO2 are absorbed into the tubular cell and react to form H2CO3
Carbonic anhydrase in the cell converts H2CO3 —-> H+ + HCO3-
H+ moves out via the Na+/H+ exchanger
HCO3- is reabsorbed into the blood

Question 13

Where does bicarbonate reabsorption take place and which areas reabsorb more bicarbonate?

Answer 13

80% takes place in the proximal convoluted tubule

20% takes place in the thick ascending limb of the loop of Henle and in the outer medullary collecting duct

Question 14

State two primary stimuli for increase in H+ secretion.

Answer 14

Decrease in plasma bicarbonate concentration

Increase in PaCO2

Question 15

State two secondary stimuli for an increase in H+ secretion.

NOTE: secondary means that it is not directed at maintaining acid-base balance

Answer 15

Angiotensin II secretion 
Aldosterone secretion 
Decrease ECF volume 
Hypokalaemia 
Increase in filtered load of bicarbonate

Question 16

How are the stimuli for a decrease in H+ secretion different?

Answer 16

They are the opposite

Question 17

Describe bicarbonate production.

Answer 17

Amino acids are broken down in the liver to produce glutamine and urea
Glutamine is taken to the kidneys and broken down to produce ammonium and alpha ketoglutarate.
Alpha-ketoglutarate is then converted to HCO3-.

Question 18

What happens to the ammonia produced in the tubular cells from the breakdown of glutamine?

Answer 18

It moves into the tubular fluid either as ammonium or as NH3 + H+
Further down the nephron, H+ will enter the tubular fluid and react with the NH3 to form NH4+

Question 19

What could cause metabolic acidosis?

Answer 19

Low pH and bicarbonate.

Addition of non-volatile acids (ketoacidosis in diabetes)
Loss of non-volatile alkalis (diarrhoea)
Failure to reabsorb sufficient HCO3- (renal failure)

Question 20

What is the most common cause of metabolic alkalosis?

Answer 20

Loss of non-volatile acids (e.g. vomiting)

raised aldosterone.

Question 21

What two things can the kidney change to compensate for respiratory acidosis or alkalosis?

Answer 21

NH4+ excretion and HCO3- reabsorption

Respiratory acidosis: increasing bicarbonate and ammonium secretion