Lecture 5: Physiology of Kidney - Acid Base Balance

Question 1

what is the normal pH of arterialised blood?

Answer 1

7.4

Question 2

define metabolic acidosis

Answer 2

• an acidosis of metabolic origin due to a decreased [HCO3-], either due to increased buffering of H+ or direct loss of HCO3-.
• to protect the pH, pCO2 must be decreased.
• presents as low pH, low HCO3- and low/normal PaCO2.

Question 3

list the causes of metabolic acidosis

Answer 3

1. increased H+ production, as in ketoacidosis of a diabetic or in lactic acidosis.
2. failure to excrete the normal dietary load of H+ as in renal failure.
3. loss of HCO3- as in diarrhoea i.e. failure to reabsorb intestinal HCO3-.

Question 4

how is metabolic acidosis compensated for?

Answer 4

• triggers hyperventilation (also known as Kussmaul’s respiration, i.e. deep and laboured breathing) to excrete more CO2.

Question 5

define metabolic alkalosis

Answer 5

• occurs when there is a raised HCO3- and a base excess (BE) > +2mmol/L in the arterial blood, leading to a high blood pH.
• presents as high pH, high/normal PaCO2 and high HCO3-.

Question 6

list the causes of metabolic alkalosis

Answer 6

• vomiting
• diuretics
• Cushing syndrome
• Conn’s syndrome
• compensation for chronic respiratory acidosis
• Bartter’s syndrome
• excess alkaline intake
• massive blood transfusions

Question 7

define respiratory acidosis

Answer 7

• pH has fallen due to a respiratory change, so PCO2 must have increased.
• results from hypoventilation and therefore the retention of CO2.
• response: protect the pH so need to increase [HCO3-].

Question 8

list the causes of respiratory acidosis

Answer 8

Acute:
- opiates
- barbiturates
- obstruction of major airways

Chronic:
- COPD
- asthma etc.

Question 9

define respiratory alkalosis

Answer 9

alkalosis of respiratory origin so must be due to a fall in PCO2 and this can occur through hyperventilation and CO2 blow-off.
- causes increased pH.
- to protect pH, [HCO3-] should decrease.

Question 10

causes of respiratory alkalosis

Answer 10

acute:
- voluntary hyperventilation
- aspirin
- first ascent to altitude

chronic:
- long-term residence at high altitude
- decrease PO2 to < 60mmHg (8kPa) stimulates peripheral chemoreceptors to increase ventilation.

Question 11

what is the normal value of pCO2

Answer 11

5.3kPa = 40mmHg

Question 12

what is the normal value of [HCO3-]?

Answer 12

24mmoles/l

Question 13

Increases in H+ in acidosis also lead to an increase in concentration of another ion?

Answer 13

K+ leads to hyperkalaemia because of need to maintain electrochemical neutrality

Question 14

how does the kidney regulate [HCO3-]?

Answer 14

1. reabsorbing filtered HCO3-
2. by generating new HCO3-

both of these processes depend on active H+ ion secretion from tubule cells into the lumen.

Question 15

pH is defined as the ratio of

Answer 15

[HCO3-]/PCO2

Question 16

The urinary system utilises two methods to alter blood pH. What are these?

Answer 16

Excretion of hydrogen (H+) ions as dihydrogen phosphate or ammonia and production and reabsorption of bicarbonate (HCO3–) ions.

Question 17

There are two methods by which hydrogen ions are excreted. What are these?

Answer 17

• Excretion of H+ ions in the form of dihydrogen phosphate (H2PO4–)
• Excretion of hydrogen ions in the form of ammonium (NH4+)

Question 18

Describe the mechanism in which H+ is excreted in the form of dihydrogen phosphate (H2PO4-).

Answer 18

• H+ ions are actively transported into the DCT lumen via hydrogen-ATPase pumps on alpha-intercalated cells.
• Excess luminal phosphate can bind a large portion of hydrogen ions, buffering them as H2PO4– before excretion.
• This excretion of H+ ions increases blood pH.

Question 19

Describe the mechanism in which hydrogen ions are excreted in the form of ammonium (NH4+).

Answer 19

• Glutamine is converted to glutamate and ammonium in the proximal convoluted tubule (PCT).
• The ammonium dissociates to ammonia and H+ ions, allowing it to pass through the membrane and enter the lumen.
• Once in the lumen, it reforms ammonium by picking up a luminal H+ ion.
• This allows hydrogen to be excreted as ammonium ions, increasing blood pH.
• Furthermore, ammonia secreted at the PCT can be used further down to buffer and excrete H+ ions secreted by alpha-intercalated cells in the collecting duct. This is due to its ability to pass membranes and traverse the nephron.

Question 20

Describe the process of Bicarbonate (HCO3-) reabsorption in the PCT.

Answer 20

• H+ ions are secreted into the lumen via the sodium-hydrogen (Na+-H+) exchanger to combine with any filtered bicarbonate. This then forms carbonic acid (H2CO3), catalysed by carbonic anhydrase on the luminal side.
• Carbonic acid then dissociates into carbon dioxide and water, which both can diffuse into the cell. Here, the reaction is undone, and carbonic anhydrase inside the cell converts carbon dioxide and water to carbonic acid, which then dissociates into H+ and HCO3– ions.
• HCO3– can then be transported into the blood whilst the H+ ions can be transported back into the lumen for the cycle to repeat.

Question 21

Describe the process of Bicarbonate (HCO3-) production.

Answer 21

• The kidney is also able to produce bicarbonate. The metabolic activity of cells produces large amounts of carbon dioxide. This then reacts with water to produce HCO3– ions, which enter the plasma, and H+ ions are transported into the lumen.
• This is useful as it also provides H+ ions to drive HCO3– reabsorption. In addition to this bicarbonate can also be produced from amino acids, which produce ammonium ions which then enter the urine.