9. H+, K+, Ca2+ And Mg2+

Question 1

Metabolism of what produced CO2?

Answer 1

Carbohydrate and fat.

Question 2

Metabolism of what produced non-carbonic acids such as ammonium, sulphuric acid and phosphoric acid?

Answer 2

Protein.

Question 3

Why do the kidneys need to re-absorb all bicarbonate before they can excrete excess H+?

Answer 3

For each bicarbonate molecule lost in urine, a H+ ion is generated.

Question 4

What does pH depend on?

Answer 4

CO2 + H2O H+ + HCO3-

Net direction depends on the concentrations of reactants and products. pH depends on how much CO2 reacts to form H+.

Question 5

What is the pH in the descending limb of the loop of Henle and collecting duct?

Answer 5

Descending loop of Henle - 6.7 (HCO3- reabsorption).

Collecting duct - variable 4.5-8.

Question 6

Where is most HCO3- recovered in the kidney?

Answer 6

Proximal convoluted tubule.

Question 7

What is H+ excretion linked to in the proximal convoluted tubule?

Answer 7

Na+ entry into the tubular cell.

Question 8

How is HCO3- reabsorbed in the proximal convoluted tubule?

Answer 8

H+ excreted via Na+/H+ exchanger reacts with HCO3- in the tubular lumen, to form H2O and CO2. There are absorbed across the apical membrane by the tubular cell, and converted back to H+ and HCO3- in the cell. The HCO3- is then absorbed across the basolateral membrane via a Na+/HCO3- cotransporter.

Question 9

What system buffers most of the excess H+ in urine?

Answer 9

Ammonia system.

Question 10

What result does vomiting have on acid-base balance?

Answer 10

Loss of H+ and loss of K+.

Metabolic alkalosis.

Question 11

What result does diarrhoea have on acid base balance?

Answer 11

Loss of K+ and HCO3-.

Metabolic acidosis.

Question 12

How is K+ taken up into cells?

Answer 12

Via 3Na+/2K+ ATPase.

Question 13

What 3 things predominantly increase 3Na+/2K+ ATPase activity and so increase K+ entry into cells?

Answer 13

K+ concentration in plasma.
Insulin.
Noradrenaline effect on beta2-adrenoceptors.

Question 14

Name 1 condition that can inhibit 3Na+/2K+ ATPase activity?

Answer 14

Digitalis (foxgloves).

Chronic disease eg heart failure, CKD.

Question 15

Give 3 things than increase K+ movement out of a cell via K+ channels?

Answer 15

High osmolarity.
Acidosis.
Cell damage.
Exercise.

Question 16

Name 1 thing than reduces K+ movement out of cells by K+ channels.

Answer 16

Alkalosis.

Question 17

Where in the nephron is most K+ reabsorbed?

Answer 17

Proximal tubule.

Question 18

Where in the nephron tubule can K+ excretion be varied?

Answer 18

Collecting duct.

Question 19

What is Liddle’s syndrome?

Answer 19

Hereditary disorder involving increased ENaC activity, causing the kidneys to excrete K+ (via ROMK) but retain too much Na+ and H2O leading to hypertension and metabolic alkalosis.

Question 20

What two things increase K+ secretion?

Answer 20

High flow.

Aldosterone.

Question 21

What is the aldosterone paradox?

Answer 21

The ability of the kidney to stimulate NaCl retention with minimal K+ secretion under conditions of volume depletion, and maximise K+ secretion without Na+ retention in hyperkalaemia. (As is able to increase Na+ retention and increase K+ secretion).

Question 22

Name 2 conditions can a diet high in K+ help protect against?

Answer 22

Hypertension.
Stroke.
Kidney stones.

Question 23

What is the minimum K+ excretion per day (as kidneys are unable to conserve all the filtered K+, unlike Na+)?

Answer 23

15 mmol/day.

Question 24

What do the symptoms of hyperkalaemia and hypokalaemia relate to?

Answer 24

Their effect on the membrane potential:
Low serum K+, bigger K+ gradient between intracellular and extracellular compartment - membrane depolarised and increased excitability.
High serum K+, smaller K+ gradient between intracellular and extracellular compartment - membrane hyperpolarised and decreased excitability.

Question 25

What affect can hyperkalaemia and hypokalaemia have on the heart? What does this risk depend on?

Answer 25

Increased risk of cardiac arrhythmias. | Risk of symptoms depends on degree and rapidity of change.

Question 26

What are the main symptoms of hypokalaemia?

Answer 26

Muscle weakness. ADH resistance leading to polyuria. Smooth muscle dysfunction leading to constipation. Arrhythmias.

Question 27

What can cause increased K+ entry into cells, therefore leading to hypokalaemia?

Answer 27

Metabolic alkalosis. | Increased beta-adrenergic activity (NA with stress).

Question 28

What can cause increased K+ GI loss, therefore leading to hypokalaemia?

Answer 28

Vomiting/NG drainage. | Diarrhoea.

Question 29

What can cause increased K+ urinary loss, therefore leading to hypokalaemia?

Answer 29

Increased aldosterone due to volume depletion (diuretics), primary hyperaldosteronism or secondary hyperaldosteronism. Increased urine flow (diuretics). Renal tubular acidosis. Magnesium deficiency.

Question 30

How would you treat a patient with hypokalaemia?

Answer 30

Oral K+ supplements and slow IV potassium.

Question 31

What acid-base or electrolyte imbalances can cause hypokalaemia?

Answer 31

Acidosis. Alkalosis. Hypomagnesaemia. Hypocalcaemia.

Question 32

What does high calcium in urine increase the risk of?

Answer 32

Kidney stones.

Question 33

What state is calcium in in the plasma?

Answer 33

Half is protein bound and half is in ionised form.

Question 34

Calcium in what state is filtered by the kidneys?

Answer 34

Ionised calcium.

Question 35

What affect does increased parathyroid hormone levels have on Ca2+ levels?

Answer 35

Increased parathyroid hormone increases Ca2+.

Question 36

What affect does increases calcitonin levels have on Ca2+ levels?

Answer 36

Increased calcitonin decreases Ca2+ levels.

Question 37

What is renal 25-hydroxyvitamin D3 1alpha-hydroxylase?

Answer 37

Cytochrome p450 enzyme found in the proximal tubule of the kidney which catalyses the hydroxylation of calcifediol to calcitriol.

Question 38

What affect does increasing calcitriol levels have on Ca2+ levels?

Answer 38

Increased calcitriol increases the level of Ca2+.

Question 39

How can Ca2+ levels be increased in the body?

Answer 39

Increased Ca2+ uptake from the gut into the blood. Increased reabsorption of Ca2+ by the kidneys. Increased mobilisation of Ca2+ from skeleton and soft bones.

Question 40

What area of the kidney nephron does parathyroid hormone and calcitriol act on?

Answer 40

Distal convoluted tubule and renal connecting tubule.

Question 41

Give 4 symptoms of hypocalcaemia.

Answer 41

Muscular eg fatigue, muscle weakness, paraesthesia (finger tips/lips), tetany, larygnospasm. Heart - reduced myocardial contractility (long QT). Neurological - irritability, memory loss, confusion, hallucination, paranoia.

Question 42

Name 3 causes of hypocalcaemia.

Answer 42

``` Vitamin D deficiency. Lack of PTH (high phosphate). Reduced intake. Malabsorption. Pancreatitis. Chronic diarrhoea. Hypercalciuria. Hyperphosphataemia. Hypomagnesaemia (interferes with PTH). ECF expansion. Acidosis. Drugs. ```

Question 43

Name 2 drugs associated with hypocalcaemia.

Answer 43

Loop diuretics. Drugs containing phosphate. Phenytoin. Drugs lowering magnesium levels eg gentamicin, cisplatin.

Question 44

Name 3 functions of Mg2+.

Answer 44

Intracellular signalling. Cofactors for protein and DNA synthesis. Control of neuronal activity in the brain. Cardiac excitability. Neuromuscular transmission. Osteoblast proliferation and bone strength.

Question 45

How much Mg2+ is usually absorbed by the gut, and how much can this increase to when levels of Mg2+ are low?

Answer 45

30-50%. | Increase to 80% of daily intake.

Question 46

What is responsible for the day-to-day fine tuning of Mg2+ levels?

Answer 46

The kidney.

Question 47

What proportion of plasma Mg2+ is filtered by the kidneys?

Answer 47

70% (other 30% bound to albumin and not filtered).

Question 48

Where in the nephron is most Mg2+ reabsorbed?

Answer 48

Thick ascending limb of the loop of Henle.

Question 49

Name two symptoms of hypomagnesaemia with a serum magnesium <0.7mmol/L.

Answer 49

Fatigue. Muscle spasms. Anxiety/depression. Headache.

Question 50

Name two symptoms of hypomagnesaemia with a serum magnesium <0.4mmol/L.

Answer 50

``` Cardiac dysrhythmias. Hyperreflexia. Tetany. Seizures. Hypokalaemia. Hypocalcaemia. ```

Question 51

What percentage of total body magnesium is serum magnesium a measure of?

Answer 51

1% of total body Mg2+.

Question 52

Name 5 causes of hypomagnesaemia, one from decreased intake, one a drug, one from GI loss, one from renal loss and one miscellaneous.

Answer 52

Decreased intake - malnutrition, prolonged fasting, IV feeding. Drugs - loop diuretics, thiazides diuretics, proton pump inhibitors, cyclosporine and tacrolimus (transplant), aminoglycosides, cisplatin. GI loss - malabsorption/short small intestine (resection), chronic diarrhoea, fistulae. Renal loss - diuretics, polyuria, hyperaldosteronism, diabetes (glycosuria or ketoacidotic states), metabolis acidosis, renal tubule defects. Miscellaneous - alcoholism, acute and chronic pancreatitis.

Question 53

How would you treat a patient with hypomagnesaemia?

Answer 53

Oral magnesium salts (GI side effects). | IV magnesium sulfate (slow infusion, otherwise cardiac arrest).

Question 54

If hypomagnesaemia present with hypokalaemia or hypocalcaemia, which needs to be treated first?

Answer 54

Hypomagnesaemia.

Question 55

When can hypermagnesaemia occur?

Answer 55

Renal impairment and adrenal insufficiency - but not symptomatic. Symptomatic - iatrogenic eg IV magnesium, purgatives/enemas, babies born to mothers treated with IV-Mg2+ eh pre-eclampsia.

Question 56

How would you treat a patient with hypocalcaemia?

Answer 56

Calcium supplementation and correct underlying cause.