Renal control of electrolytes and acid base balance

Question 1

Describe renal calcium handling and what hormones are involved

Answer 1

Ca 2+ plays many major roles: muscular contraction, neurotransmitter released, blood coagulation, cell division and bone
formation.

 99% of the body’s Ca
2+ is in bone and only 0.1% in plasma.
 Normal plasma [Ca2+]: 2.5 mmol/L, of which 50% is ionised and the remainder bound to plasma proteins.
o Low plasma [Ca2+] (hypercalcaemia) increases the excitability of nerve and muscle cells, causing muscular spasms
and increasing the risk of cardiac arrhythmias.
2. Hormonal regulation of plasma [𝐂𝐚𝟐+]

2.1. PTH (parathyroid hormone)
 Secreted by the parathyroid glands in response to a low plasma [Ca
2+] and acts to:
o Increase Ca
2+ reabsorption by the kidneys.
o Stimulate bone resorption of Ca
2+.
o Stimulate production of calcitriol

2.2. Calcitriol (1,25 dihydroxycholecalciferol) (𝟏, 𝟐𝟓 (𝐎𝐇)𝟐 vitamin 𝐃𝟑)
 Calcitriol is an active product of cholecalciferol (vitamin D3
). Cholecalciferol is taken
in the diet and is also generated in the skin by the action of UV light.
 Calcitriol stimulates Ca
2+ uptake from the gut and increases bone resorption.

3. Renal calcium handling
 Ca
2+ is reabsorbed along the length of the nephron, mainly in the proximal tubule,
but also in the TALH and distal tubule.
 PTH increases Ca
2+ reabsorption in the TALH and distal tubule.
 Calcitriol increases Ca
2+ reabsorption in the distal tubule.

Question 2

Describe renal phosphate handling

Answer 2

Normal plasma [phosphate]: 1-2 mmol/L.
 Plasma phosphate represents 0.03% of total phosphate.
 Phosphate reabsorption in the kidneys takes place almost exclusively
in the proximal tubule, using Na
+-phosphate co-transporters.
 Dietary phosphate directly affects the number of apical transporters.
 PTH increases phosphate loss by inhibiting reabsorption.

Question 3

Describe renal potassium handling

Answer 3

Most important cation in determining membrane voltage, so is
highly regulated.
 Cortical collecting duct corrects any imbalances in the body, because
any prior absorbed K
+ is already re-absorbed into the body.

1. Regulation of plasma potassium
    Maintenance of K
   + is through excretion, as intake is uncontrolled.
    98% of K
   + is intracellular, but regulation of extracellular [K
   +] is also
   important because it is a principle determinant of the membrane
   potential of excitable cells.
   o Normal range: 3.5-5.0 mmol/l.
   o Values outside the range (2-8 mmol/L) can lead to cardiac arrhythmia.
2. Factors affecting plasma potassium concentration
   Insulin: stimulates K
   + uptake into cells, therefore reducing plasma [K
   +]. Rise in plasma [K
   +] after a K
   + rich meal is greatest
   in people with diabetes mellitus.
    Aldosterone:
   o Pathological increases in aldosterone secretion (e.g. primary hyperaldosteronism) decreases plasma [K
   +].
   o Pathological decrease in aldosterone secretion (e.g. Addison’s disease) increases plasma [K
   +].
    Diuretics: loop diuretics and thiazides, by increasing tubular flow and Na
   + delivery to the distal nephron increases K
   +
   secretion and reduces plasma [K+].
    Acid-base status:
   o Alkalosis reduces plasma [K
   +] by increasing K
   + secretion in the distal nephron.
   o Acute acidosis has the opposite effect.
   o Chronic acidosis, by reducing proximal tubular reabsorption, increases distal tubular flow and rate and thus
   stimulates K+ secretion, offsetting the direct inhibitory effect of the lowered pH.
    Cell lysis/tissue trauma: release of intracellular fluids (e.g. burns, crush injuries, haemolysis) will increase plasma [K+].
    Renal failure: severe renal failure, in which K
   + cannot be adequately excreted, is the most common cuse of raised plasma
   [K+].

Question 4

What are the factors affecting K+ secretion

Answer 4

Aldosterone: ↑ Na
+ reabsorption  Depolarises apical membrane  ↑ K
+ secretion
 Dietary 𝐊
+:
o High K
+ intake  ↑ plasma aldosterone and ↑ uptake at basolateral membrane  ↑ K
+ secretion
o Low K
+ intake  Stimulates H
+/K
+ pump in α-intercalated cells
 Tubular flow rate: high flow rate and Na
+ delivery (e.g. diuretics) stimulates secretion  Hypokalaemia
 Acid-base balance:
o Alkalosis  ↑ activity of apical K
+ channels  Hypokalaemia
o Acidosis (acute)  ↓ activity of apical K
+ channels  Hyperkalaemia

Question 5

How does acid base regulation work

Answer 5

Arterial pH: 7.35-7.45

 50 mmol/day of non-volatile acids are produced from metabolism. These need to be removed, or a buffer used, otherwise if
they were distributed across the total body water (50 litres), pH = 3, and the minimum pH compatible with life is 6.8.

Question 6

Describe some chemical buffers

Answer 6

H+ depletes the buffer anion, so the anion needs to be replenished.
 Only the HCO3
− system can be controlled physiologically. All the other buffer systems are in equilibrium with each other, so
there is only need to control one system.
1. Bicarbonate buffer system
 pH = pK + log [HCO3−]/[CO2]
= pK + log [HCO3−]
0.03×pCO2
 pH =∝
[HCO3−]
pCO2

2. Renal control of plasma bicarbonate
 Reabsorption of filtered HCO3
−.
 Addition of new HCO3
− to plasma: to replace the lost HCO3
− in acid base balance.

Question 7

Describe the different acid base disorders

Answer 7

Respiratory acidosis:
o Example: bronchitis
o Hypoventilation ↑ pCO2  ↓ pH
 Respiratory alkalosis:
o Example: high altitude.