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

5 - 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

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

Answer 9

Proximal convoluted tubule
Thick ascending limb of the loop of Henle
Alpha intercalating cell of the outer medullary collecting duct

Question 10

What transporters are involved in the renal excretion of H+ and reabsorption of HCO3- in the proximal convoluted tubule and in the collecting duct?

Answer 10

PCT
Na+/H+ exchanger, H+ ATPase (apical membrane)
HCO3-/Na+ cotransporter, Na+/K+ ATPase, HCO3-/Cl- exchanger (basolateral membrane)

Collecting Duct
Alpha cell:
Na+/H+ exchanger, H+ ATPase, K+/H+ ATPase (apical membrane)
Cl-/HCO3- exchanger (basolateral membrane)
Beta cell:
Same transporters on the opposite membranes

Question 11

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

Answer 11

Bicarbonate is unable to enter the cell.
H+ goes out of the cell into the filtrate.
H+ reacts with HCO3- in the filtrate to form H2CO3.
Carbonic anhydrase converts H2CO3 to H2O + CO2.
H2O + CO2 can then diffuse into the tubular cell and react to form H2CO3.
Carbonic anhydrase in the cell converts H2CO3 —-> H+ + HCO3-.
H+ moves out again into the filtrate and HCO3- is reabsorbed into the blood

Question 12

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

Answer 12

80% takes place in the proximal convoluted tubule
10% takes place in the thick ascending limb of the loop of Henle
6% takes place in the distal convoluted tubule 4% takes place in the outer medullary collecting duct

Question 13

State two primary stimuli for increase in H+ secretion.

Answer 13

Decrease in plasma bicarbonate concentration

Increase in PaCO2

Question 14

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

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

Answer 14

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

Question 15

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

Answer 15

They are the opposite

Question 16

Describe bicarbonate production by cells.

Answer 16

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 17

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

Answer 17

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 18

What could cause metabolic acidosis?

Answer 18

Addition of non-volatile acids

Loss of non-volatile alkalis - uncontrolled diabetes

Question 19

What is the most common cause of metabolic alkalosis?

Answer 19

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

Question 20

What are the acute and chronic compensatory mechanisms for respiratory acidosis and alkalosis?

Answer 20

Acute = intracellular buffering.
Chronic = altered bicarbonate reabsorption and ammonium excretion.

Question 21

What is the significance of bicarbonate?

Answer 21

It is a high capacity chemical buffer which can respond rapidly to changes in metabolic acid and can be produced from volatile respiratory acid

Question 22

Henderson-Hasselbach equation

Answer 22

pH = pKa + log10[HCO3-]/[CO2]