S6) Regulation of Ions

Question 1

With reference to the CO₂ / HCO₃^- buffer system, explain the control of blood pH

Answer 1

pH depends on how much CO₂ reacts to form H⁺:

• [CO₂]_dissolved pushes reaction to right
• [HCO₃^-] pushes reaction to left

Question 2

Briefly describe how pH varies along the nephron

Answer 2

Question 3

HCO₃^- is filtered at the glomerulus but ~ 80% recovered in PCT.

Describe how the renal recovery of bicarbonate occurs

Answer 3

• H⁺ excretion linked to Na⁺ entry in PCT
• H⁺ reacts with HCO₃^- in the lumen to form CO₂ which enters cell
• Converted back to HCO₃^- which enters ECF

Question 4

Identify the two buffers for H⁺ excretion in the kidney

Answer 4

• HPO₄^2- (or some titratable acid)
• NH₄⁺

Question 5

Illustrate the role of NH₄⁺ in the H⁺ buffering systems in the kidney

Answer 5

Question 6

Illustrate the role of HPO₄^2- in the H⁺ buffering systems in the kidney

Answer 6

Question 7

Loss of Cl^- and K⁺ have a synergistic effect on alkalosis.

Explain why this is

Answer 7

• Normally, kidneys respond rapidly to increased HCO₃^- by excreting the excess
• Sustained alkalosis occurs when something else disrupts renal regulation of alkali (potassium & chloride)

Question 8

Distinguish between the acid-base status after vomiting and diarrhoea respectively

Answer 8

• Vomiting: loss of H⁺ and K⁺ → metabolic alkalosis
• Diarrhoea: loss of K⁺ and HCO₃^- → metabolic acidosis

Question 9

Explain how the inhibited Cl^- and K⁺ reabsorption by furosemide contributes to chloride, sodium, potassium and water loss

Answer 9

Question 10

How would one treat a 66 year old man taking furosemide with metabolic alkalosis and a 2 day history of vomiting and diarrhoea?

Answer 10

• Stop furosemide diuretic
• Replace NaCl
• Replace KCl

Question 11

Approximately 98% of total body K⁺ is found in cells.

Identify 5 organs/compartments where K⁺ is largely distributed

Answer 11

• Muscle (most)
• Liver
• Interstitial fluid
• Red blood cells
• Plasma (least)

Question 12

What is the normal [K⁺]_plasma ?

Answer 12

Serum potassium = 4 mmol/L

Question 13

What is the recommended daily intake of potassium?

Answer 13

Average daily intake 40 – 100 mmol / day

Question 14

What prevents the toxic accumulation of ingested K⁺ in the extracellular compartment?

Answer 14

• K⁺ uptake into cells (quick)
• K⁺ excretion in urine (6-8 hours)

Question 15

How much potassium is lost in urine?

Answer 15

80-90% lost in urine (remainder in faeces / sweat)

Question 16

3 Na⁺ / 2 K⁺ ATPase facilitates potassium uptake into cells.

Which 3 factors/events increase and decrease its activity?

Answer 16

• Increased by: insulin, β2 receptor agonists, noradrenaline, aldosterone, [K⁺]_plasma
• Decreased by: digitalis, chronic disease (heart failure, CKD)

Question 17

Which factors increase and decrease potassium excretion from cells?

Answer 17

• Increased by: high osmolality, acidosis, cell damage, exercise
• Decreased by: alkalosis

Question 18

Briefly, describe the renal regulation of [K⁺]_plasma

Answer 18

[K⁺]_plasma is regulated by excretion not absorption

Question 19

Where in the kidney nephron is potassium reabsorbed?

Answer 19

• 65 – 70% PCT (paracellular)
• 20 – 25% TAL (transcellular)

Question 20

Describe the mechanisms driving K⁺ transport in the DCT

Answer 20

Question 21

Describe the mechanisms driving K⁺ secretion in CD

Answer 21

Question 22

Describe the mechanisms driving K⁺ reabsorption in the collecting duct

Answer 22

Question 23

Illustrate the variable K⁺ excretion based on [K⁺]_plasma

Answer 23

Question 24

How does aldosterone act to increase K⁺ secretion?

Answer 24

• ↑ [K⁺]_{intracellular}
• ↑ electronegative lumen (Na⁺ reabsorption)
• ↑ permeability of luminal membrane

Question 25

What is the aldosterone paradox?

Answer 25

The **aldosterone paradox** is the ability of the kidney to: - Stimulate NaCl retention without increased K⁺ secretion (during volume depletion) - Maximise K⁺ secretion without Na⁺ retention (during hyperkalemia)

Question 26

What are the benefits of diets high in K⁺?

Answer 26

- Lower BP - Reduced stroke risk - Reduced risk of kidney stones

Question 27

What are the effects of hypokalaemia?

Answer 27

- Low serum K⁺ leads to **bigger K⁺ gradient** between intracellular and extracellular compartment - **Increased excitability** (& risk of arrhythmia)

Question 28

What are the effects of hyperkalaemia?

Answer 28

- High serum K⁺ leads to **smaller K⁺ gradient** between intracellular and extracellular compartment - **Decreased membrane excitability** (& risk of arrhythmias)

Question 29

What are the symptoms of hypokalaemia?

Answer 29

- Weakness - Polyuria (ADH resistance) - Constipation (smooth muscle dysfunction) - Arrhythmias

Question 30

What are the 4 possible causes of hypokalaemia?

Answer 30

- Reduced dietary intake - Increased entry into cells (metabolic alkalosis, ↑ β-adrenergic activity) - Increased GI loss (vomiting, diarrhoea) - Increased urine loss (↑ aldosterone)

Question 31

How does one assess a patient with hypokalaemia?

Answer 31

- History - Fluid balance - Acid base status - Urine K⁺ excretion (if K⁺ loss unclear)

Question 32

What is the general treatment of hypokalaemia?

Answer 32

- Oral K⁺ supplements - Slow IV potassium

Question 33

In terms of hypokalaemia, what happens when one electrolyte abnormality present does not respond to treatment?

Answer 33

Consider other the effect of other acid-base or electrolyte imbalances: - Acidosis - Alkalosis - Hypomagnesaemia - Hypocalcaemia

Question 34

State three functions of calcium

Answer 34

- Strength of bones and teeth - Important for nerve and muscle function - Concentration determines action potential

Question 35

Briefly, describe how calcium is distributed in extracellular and intracellular spaces

Answer 35

Question 36

Outline the mechanisms involved which prevent hypercalcaemia

Answer 36

Question 37

Outline the mechanisms involved which prevent hypocalcaemia

Answer 37

Question 38

Describe the principles of calcium resorption in different parts of the kidney nephron

Answer 38

- **PCT**: paracellular - **TAL**: transcellular - **DCT**: transcellular (PTH & vitamin D control) - **CT**: not reabsorbed

Question 39

Point out some neurological and muscular symptoms of hypocalcaemia

Answer 39

- **Neurological**: irritability, memory loss, confusion, hallucination - **Muscular**: fatigue, muscle weakness, paraesthesia, tetany, reduced myocardial contractility (long QT)

Question 40

Identify 5 causes of hypocalcaemia

Answer 40

- Vitamin D deficiency - Lack of PTH (high phosphate) - Reduced intake - Malabsorption - Chronic diarrhoea

Question 41

Identify 4 drugs which are associated with hypocalcaemia

Answer 41

- Loop diuretics - Drugs containing phosphate - Phenytoin - Drugs that lower magnesium levels *e.g. gentamicin, cisplatin*

Question 42

How can one treat hypocalcaemia due to Vitamin D deficiency?

Answer 42

- Vitamin D supplementation - Calcium supplementation

Question 43

Briefly, describe how magnesium is distributed in intracellular and extracellular spaces

Answer 43

Question 44

State five functions of magnesium

Answer 44

- Intracellular signalling - Cofactor for protein & DNA synthesis - Control of neuronal activity in the brain - Cardiac excitability - Neuromuscular transmission

Question 45

Briefly illustrate how [Mg²⁺] in the body is maintained through homeostasis

Answer 45

Question 46

When GFR normal, up to 2400 mg Mg²⁺ is filtered per day. Describe the kidney handling of magnesium

Answer 46

- 10 – 25% **PCT** - 50 – 70% **TAL** - 5 – 10% **DCT**

Question 47

Hypomagnesaemia is when serum magnesium \< 0.7 mmol/L. What are the symptoms of such?

Answer 47

- **\< 0.7 mmol/L:** fatigue, muscle spasms, anxiety, headache, depression - **\< 0.4 mmol/L:** cardiac dysrhythmias, hyperreflexia, tetany, seizures, hypokalaemia & hypocalcaemia

Question 48

Identify 5 causes of hypomagnesaemia

Answer 48

- Decreased intake (malnutrition / prolonged fasting) - Malabsorption - Chronic diarrhoea - Hyperaldosteronism - Diabetes (glycosuria / ketoacidotic states)

Question 49

Identify 4 drugs which are associated with hypomagnesaemia

Answer 49

- Loop diuretics - Thiazide diuretics - Proton pump inhibitors - Aminoglycosides

Question 50

Describe the general treatment of hypomagnesaemia

Answer 50

- Oral magnesium salts (GI side effects) - IV magnesium sulfate (slow infusion to prevent cardiac arrest)

Question 51

Hypermagnesaemia is uncommon. When does it occur?

Answer 51

Occurs with **renal impairment** and **adrenal insufficiency** (asymptomatic)

Question 52

Describe the general treatment of hypermagnesaemia

Answer 52

- Iv magnesium - Purgatives / enemas