S6) Regulation of Ions Flashcards
With reference to the CO2 / HCO3- buffer system, explain the control of blood pH
pH depends on how much CO2 reacts to form H+:
- [CO2]dissolved pushes reaction to right
- [HCO3-] pushes reaction to left
Briefly describe how pH varies along the nephron
HCO3- is filtered at the glomerulus but ~ 80% recovered in PCT.
Describe how the renal recovery of bicarbonate occurs
- 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
Identify the two buffers for H+ excretion in the kidney
- HPO42- (or some titratable acid)
- NH4+
Illustrate the role of NH4+ in the H+ buffering systems in the kidney
Illustrate the role of HPO42- in the H+ buffering systems in the kidney
Loss of Cl- and K+ have a synergistic effect on alkalosis.
Explain why this is
- Normally, kidneys respond rapidly to increased HCO3- by excreting the excess
- Sustained alkalosis occurs when something else disrupts renal regulation of alkali (potassium & chloride)
Distinguish between the acid-base status after vomiting and diarrhoea respectively
- Vomiting: loss of H+ and K+ → metabolic alkalosis
- Diarrhoea: loss of K+ and HCO3- → metabolic acidosis
Explain how the inhibited Cl- and K+ reabsorption by furosemide contributes to chloride, sodium, potassium and water loss
How would one treat a 66 year old man taking furosemide with metabolic alkalosis and a 2 day history of vomiting and diarrhoea?
- Stop furosemide diuretic
- Replace NaCl
- Replace KCl
Approximately 98% of total body K+ is found in cells.
Identify 5 organs/compartments where K+ is largely distributed
- Muscle (most)
- Liver
- Interstitial fluid
- Red blood cells
- Plasma (least)
What is the normal [K+]plasma ?
Serum potassium = 4 mmol/L
What is the recommended daily intake of potassium?
Average daily intake 40 – 100 mmol / day
What prevents the toxic accumulation of ingested K+ in the extracellular compartment?
- K+ uptake into cells (quick)
- K+ excretion in urine (6-8 hours)
How much potassium is lost in urine?
80-90% lost in urine (remainder in faeces / sweat)
3 Na+ / 2 K+ ATPase facilitates potassium uptake into cells.
Which 3 factors/events increase and decrease its activity?
- Increased by: insulin, β2 receptor agonists, noradrenaline, aldosterone, [K+]plasma
- Decreased by: digitalis, chronic disease (heart failure, CKD)
Which factors increase and decrease potassium excretion from cells?
- Increased by: high osmolality, acidosis, cell damage, exercise
- Decreased by: alkalosis
Briefly, describe the renal regulation of [K+]plasma
[K+]plasma is regulated by excretion not absorption
Where in the kidney nephron is potassium reabsorbed?
- 65 – 70% PCT (paracellular)
- 20 – 25% TAL (transcellular)
Describe the mechanisms driving K+ transport in the DCT
Describe the mechanisms driving K+ secretion in CD
Describe the mechanisms driving K+ reabsorption in the collecting duct
Illustrate the variable K+ excretion based on [K+]plasma
How does aldosterone act to increase K+ secretion?
- ↑ [K+]intracellular
- ↑ electronegative lumen (Na+ reabsorption)
- ↑ permeability of luminal membrane
What is the aldosterone paradox?
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)
What are the benefits of diets high in K+?
- Lower BP
- Reduced stroke risk
- Reduced risk of kidney stones
What are the effects of hypokalaemia?
- Low serum K+ leads to bigger K+ gradient between intracellular and extracellular compartment
- Increased excitability (& risk of arrhythmia)
What are the effects of hyperkalaemia?
- High serum K+ leads to smaller K+ gradient between intracellular and extracellular compartment
- Decreased membrane excitability (& risk of arrhythmias)
What are the symptoms of hypokalaemia?
- Weakness
- Polyuria (ADH resistance)
- Constipation (smooth muscle dysfunction)
- Arrhythmias
What are the 4 possible causes of hypokalaemia?
- Reduced dietary intake
- Increased entry into cells (metabolic alkalosis, ↑ β-adrenergic activity)
- Increased GI loss (vomiting, diarrhoea)
- Increased urine loss (↑ aldosterone)
How does one assess a patient with hypokalaemia?
- History
- Fluid balance
- Acid base status
- Urine K+ excretion (if K+ loss unclear)
What is the general treatment of hypokalaemia?
- Oral K+ supplements
- Slow IV potassium
In terms of hypokalaemia, what happens when one electrolyte abnormality present does not respond to treatment?
Consider other the effect of other acid-base or electrolyte imbalances:
- Acidosis
- Alkalosis
- Hypomagnesaemia
- Hypocalcaemia
State three functions of calcium
- Strength of bones and teeth
- Important for nerve and muscle function
- Concentration determines action potential
Briefly, describe how calcium is distributed in extracellular and intracellular spaces
Outline the mechanisms involved which prevent hypercalcaemia
Outline the mechanisms involved which prevent hypocalcaemia
Describe the principles of calcium resorption in different parts of the kidney nephron
- PCT: paracellular
- TAL: transcellular
- DCT: transcellular (PTH & vitamin D control)
- CT: not reabsorbed
Point out some neurological and muscular symptoms of hypocalcaemia
- Neurological: irritability, memory loss, confusion, hallucination
- Muscular: fatigue, muscle weakness, paraesthesia, tetany, reduced myocardial contractility (long QT)
Identify 5 causes of hypocalcaemia
- Vitamin D deficiency
- Lack of PTH (high phosphate)
- Reduced intake
- Malabsorption
- Chronic diarrhoea
Identify 4 drugs which are associated with hypocalcaemia
- Loop diuretics
- Drugs containing phosphate
- Phenytoin
- Drugs that lower magnesium levels e.g. gentamicin, cisplatin
How can one treat hypocalcaemia due to Vitamin D deficiency?
- Vitamin D supplementation
- Calcium supplementation
Briefly, describe how magnesium is distributed in intracellular and extracellular spaces
State five functions of magnesium
- Intracellular signalling
- Cofactor for protein & DNA synthesis
- Control of neuronal activity in the brain
- Cardiac excitability
- Neuromuscular transmission
Briefly illustrate how [Mg2+] in the body is maintained through homeostasis
When GFR normal, up to 2400 mg Mg2+ is filtered per day.
Describe the kidney handling of magnesium
- 10 – 25% PCT
- 50 – 70% TAL
- 5 – 10% DCT
Hypomagnesaemia is when serum magnesium < 0.7 mmol/L.
What are the symptoms of such?
- < 0.7 mmol/L: fatigue, muscle spasms, anxiety, headache, depression
- < 0.4 mmol/L: cardiac dysrhythmias, hyperreflexia, tetany, seizures, hypokalaemia & hypocalcaemia
Identify 5 causes of hypomagnesaemia
- Decreased intake (malnutrition / prolonged fasting)
- Malabsorption
- Chronic diarrhoea
- Hyperaldosteronism
- Diabetes (glycosuria / ketoacidotic states)
Identify 4 drugs which are associated with hypomagnesaemia
- Loop diuretics
- Thiazide diuretics
- Proton pump inhibitors
- Aminoglycosides
Describe the general treatment of hypomagnesaemia
- Oral magnesium salts (GI side effects)
- IV magnesium sulfate (slow infusion to prevent cardiac arrest)
Hypermagnesaemia is uncommon.
When does it occur?
Occurs with renal impairment and adrenal insufficiency (asymptomatic)
Describe the general treatment of hypermagnesaemia
- Iv magnesium
- Purgatives / enemas
