Renal Physiology: Potassium & Magnesium (Zoysa) Flashcards
What are the key roles of the kidney?
- Elimination of waste products
- Control of fluid balance
- Control of minerals
- Regulate acid-base balance
- Produce hormones
Where is Magnesium found in our body?
99% Mg2+ found in bone (hydroxyapatite), muscle and soft tissue
- Intracellular [Mg2+] range from 5 to 20mmol/L
- Extracellular [Mg2+] accounts for 1%
What is Magneisum responsible for?
Magnesium is responsible for:
- Bone formation
- _Co-facto_r in >300 enzymatic reactions (ATP metabolism, muscle contraction and relaxtion, neurological function, release of neurotransmitters)
- Regulation of vascular tone
- Cardiac rhythm
- Platelet activated thrombosis
In humans, hydrated Mg2+ bind tightly to _______________, therefore_________________________________
In humans, hydrated Mg2+ bind tightly to many water molecules, therefore it has a big diameter and difficult to travel through intracellular channels.
It often needs to be stripped of water molecules to travel through channels (active processes).
Where do we get our Magneisum from and where do we absorb it in our system
Daily dietary intake requirement is ~300mg Mg2+.
- Some content in water, depending on how water is processed (low content in NZ).
- High content in plants, e.g. green leafy vegetables, cereals and nuts.
- Intermediate content in meat and fish
- Low content in dairy products
Mg2+ absorption occurs mostly in small intestine via paracellular receptor channels.
Describe the Reabsorption and Excretion of Magnesium
Kidney plays a key role in terms of serum Mg2+ regulation (reabsorption and excretion).
- ~2400mg is filtered by the glomeruli
- 95% immediately reabsorbed (10-20% proximal convoluted tubule, 60-70% thick ascending limb of Henle, 10% distal convoluted tubule)
- 5% (100mg) excreted in the urine
-
Proximal Convoluted Tubule
- In proximal convoluted tubule, 10-20% Mg2+ is reabsorbed via paracellular mechanism (unknown Mg2+ paracellular channels).
- There is possible involvement of Na/K ATPase (Mg2+ follows Na+)?
- In proximal convoluted tubule, 10-20% Mg2+ is reabsorbed via paracellular mechanism (unknown Mg2+ paracellular channels).
-
Thick Ascending Limb
- In thick ascending limb of Henle, _60-70% Mg2+ i_s reabsorbed via paracellular mechanism (Claudin 16-19 channels).
- Water is reabsorbed in descending limb, which drives electrolytes reabsorption in ascending limb (due to increased electrolyte concentration after water is reabsorbed)
-
There is involvement of claudin 16-19, NKA, NKCC2, ROMK and CLC-Kb with Bartin to drive Mg2+ reabsorption.
- NKCC2 mutations lead to hypomagnesaemia, hypokalemia, such as Bartter’s syndrome and Gitelman’s syndrome.
- Claudin 16-19 mutations lead to hypomagnesaemia (unable to reabsorb Mg2+ so low serum Mg2+)
- In thick ascending limb of Henle, _60-70% Mg2+ i_s reabsorbed via paracellular mechanism (Claudin 16-19 channels).
-
Distal Convoluted Tubule
- In distal convoluted tubule, 10% Mg2+ is reabsorbed via transcellular mechanism (active transport) (TRPM6, EGFR, HNF1B, CNNM2).
-
TRPM6 (transient receptor potential ion channels) are very important for Mg2+ reabsorption.
- TRPM6 mutations lead to hyomagnesaemia and hypercalcemia (formation of calcium stones in neonates).
How do you assess serum Mg concentrations?
- Serum [Mg2+] (0.7-1mmolL) (tightly regulated)
- Red cell [Mg2+] (sometimes serum [Mg2+] are not good overall markers)
- _24 hour excretio_n
- (more Mg2+ excretion nocturnally, therefore important for 24 hour test)
- _Mg2+ retention tes_t (if [Mg2+] do not rise via oral route, then absorption problem)
- Isotope analysis (not often used clinically)
What are some symptoms of Hypomagnesaemia?
- Initially
- Weakness and fatigue
- Later
- Fasciculation and cramps
- Tetany and carpopedal spasm
- Numbness (paresthesiae)
- Seizures
- Arrhythmias
What are some casues of Hypomagnesaemia
- Decreased dietary intake
- GI malabsorption and loss
- Endocrine, e.g. hyperaldosteronism, DM, SIADH, ‘hungry bone’ syndrome
- Renal loss
- Congenital
- Acquired
- Drug-induced
- (increase magnesium loss), e.g. aminoglycosides, amphotericin B, CNI, cisplatin, cetuximab, proton pump inhibitors (omeprazole), pentamidine, foscarnet
How do you treat hypomaynesaemia?
- Treatment of primary cause!
- Oral magnesium (used in most cases)
- IV magnesium (magnesium sulphate)
What can cause Hypermagnesamia?
- Very uncommon
- In advanced CKD, compensatory mechanisms start to become inadequate and hypermagesaemia may develop (although this may be balanced by decreased Mg2+ intake)
- Excessive oral administration of Mg2+ salts or Mg2+-containing drugs (e.g. milk of Mg2+)
- Iatrogenic
Potassium is the most abundant cation in ___________\_
Potassium is the most abundant cation in intracellular fluid.
Describe the Homeostasis of Potassium
- Where we get it from
- What influences its homeostasis
- How we excrete it
Potassium daily oral intake is 1560-5850mg/day.
At healthy steady state, 90-95% excreted in urine, 5-10% in faeces.
-
Kidney is primarily responsible for maintaining total body K+
- K+ freely filtered in glomerulus
- K+ reabsorption occurs in proximal convoluted tubule (60%), thick ascending limb of Henle (30%), distal convoluted tubule (variable) and collecting ducts (variable).
- Initial changes in extracellular K+ are buffered by K+ movement into or out of skeletal muscle regulated by insulin and catecholamines
It is affected by:
- Tonicity (hyperglycemia drives K+ efflux, e.g. diabetic ketoacidosis (DKA), hyperosmolar non-ketotic hyperglycaemia (HONK))
- pH (acidosis drives K+ efflux, alkalosis drives K+ influx)
What might lead to hyperkaelmia?
It is affected by:
-
Tonicity
- (hyperglycemia drives K+ efflux, e.g. diabetic ketoacidosis (DKA), hyperosmolar non-ketotic hyperglycaemia (HONK))
-
pH
- (acidosis drives K+ efflux, alkalosis drives K+ influx)
Describe the regulation of potassium via kidney
In proximal convoluted tubule, 60% K+ is reabsorbed via paracellular mechanism (driven by Na/K ATPase).
In thick ascending limb of Henle, 30% K+ is reabsorbed via transcellular and paracellular mechanism
- Passive K+ reabsorption via paracellular pathway via electrochemical gradient.
- Secondary active K+ reabsorption via NKCC2, driven by Na/K ATPase.
At distal convoluted tubules, it is regulated by aldosterone and angiotensin
- Serum potassium load (excess) stimulates aldosterone production.
- Serum sodium depletion or extracellular volume depletion stimulates renin production, which leads to increased aldosterone
What Affects Serum [K+]?
Serum [K+] is affected by
(1) K+ intake;
(2) K+ losses;
(3) K+ redistribution from ECF in/out of cells
When are people deemed to be ‘hypokaelmic’?
Symptoms of Hypokalemia
Hypokalemia is serum [K+] <3.5mmol/L.
Symptoms include:
- Muscle weakness
- Paralysis
- Cardiac conduction abnormalities
- Cramp
- Constipation
What are the symptoms of Hypokalaemia?
Symptoms of Hypokalemia
Hypokalemia is serum [K+] <3.5mmol/L. Symptoms include:
- Muscle weakness
- Paralysis
- Cardiac conduction abnormalities (e.g. palpatations)
- Cramp
- Constipation
Describe the Hypokalemimc Periodic Paralysis
Hypokalemic Periodic Paralysis
Hypokalemic period paralysis is autosomal dominant (rare) or thyrotoxic conditions
- There is _abnormal K+ channel_s on cell membrane
- This is often triggered by high carbohydrate meal (insulin) or SNS activation (b-agonist), e.g. anxiety or exercise
- This leads to _excessive movement of K+ into cell_s, results in extreme weakness
What are some causes of Potassium Loss? (Hypokaelemia)
Causes of Hypokalemia (Potassium Loss)
Renal Loss
- Renal tubular acidosis
-
Hyperaldosteronism
- Conn’s syndrome is due to adrenal adenoma (tumor), which secretes aldosterone
- Presents with hypertension and hypokalaemia
-
Licorice
- Licorice contains glycyrrhizin, which acts like aldosterone by activating mineralocorticoid receptors in kidney
- Results in hypertension and hypokalaemia
- This is termed pseudohyperaldosteronism
-
Diuretics (either increase/decrease [K+] depends on drugs)
- Hypokalaemia is caused by drugs that act more proximally (e.g. mannitol, frusemide, bumetanide)
Gut Loss
- Vomiting
- Diarrhoea (e.g. laxatives)
- Ileostomy
- Bowel fistulae
- NG tube losses
Describe the treatment of hypokalemia
- Treat the underlying problem!
- In mild hypokalemia, use oral K+
- In severe hypokalemia (<3mmol/L), use IV K+ replacement
When is someone deemed to have “hyperkalemia”?
Hyperkalemia is serum [K+] >5mmol/L.
Symptoms include:
- Fatigue or weakness
- Paraesthesia
- Nausea or vomiting
- Dyspnoea
- Palpitations
Severe hyperkalemia is an emergency, due to action potential widening (PR prolongation, wide QRS, peaked T waves), can develop into ventricular fibrillation and cardiac arrest.
What are the symptoms of hyperkalemia?
Hyperkalemia is serum [K+] >5mmol/L.
Symptoms include:
- Fatigue or weakness
- Paraesthesia
- Nausea or vomiting
- Dyspnoea
- Palpitations
_Severe hyperkalemia is an emergen_cy, due to action potential widening (PR prolongation, wide QRS, peaked T waves), can develop into ventricular fibrillation and cardiac arrest.
Describe Pseudohyperkalemima
Occasionally, pseudohyperkalemia is seen on lab tests due to haemolysed sample.
Exclusion by no symptoms, unlikely to be proper problem, repeat test if possible.
What are some causes of hyperkalemia?
-
Increased intake
- (harder if normal excretion mechanism, but easier in CKD)
-
Disruption of cell intake
- (e.g. beta blockers, acidosis, rhabdomyolysis)
- _Decreased excretio_n
- (e.g. renal failure, hypoaldosteronism, ACEi/ARB, other drugs)
Describe Addison’s Disease
- Characterisitics
- Symptoms
- Lab results
- Diagnostic test
- Treatment
Addison’s disease is deficient secretion of adrenocortical hormone (aldosterone, cortisol). Symptoms include:
- Characteristic h_yperpigmented/tanned appearance_ (due to excessive ACTH excretion, stimulating melanocytes)
- Lethargy and weakness
- Weight loss,
- Hypotension
Laboratory tests show hyperkalemia, hyponatremia
Diagnosis via short synacthen test (check cortisol production) and scans
Treatment is dexamethasone, fludrocortisone
Describe the treatment of hyperkalemia
1) Stabilise action potential
- (calcium gluconate normalize membrane excitability prevent cardiac arrest) (short term ~0.5hr)
2) Push K+ into cells
-
Beta Agonists
- Use ventolin nebulisers (5mg salbumatomol nebulized). Can do it hourly.
- Reduces K+ by 0.9-1.5mmol/L by driving K+ intracellularly
- Takes about 0.5-1hr to act
- Duration of effect 4-6hr
- Insulin
- Use 10 units short acting insulin and 50ml 50% dextrose over 10 mins
- Takes about 10–20min to act
- Peak effect 30-60min
- Duration of effect 4-6hr
- Remember dextrose bolus!
-
Treat Acidosis
- Oral bicarbonate tablets 840mg bd/tds
- IV bicarbonate 8.4% 50mL over 1hr and repeat (in emergency)
3) Reduce Absorption
- Cation exchange products such as calcium resonium 15g tds (oral or rectal)
- Bind to K+ in gut and increase faecal elimination
- Takes about 4-6hr to act
- Side effect of constipation, give with laxative
4) Increase Elimination
- K losing diuretic drugs
- Dialysis (particularly if already a dialysis patient, or if rhabdomyolosis)
5) Fix underlying problem
(Summary of Magnesium and Potassium)
Summary
Magnesium
- A common cation.
- Hypomagnesaemia is common.
- Can be due to GI, endocrine or renal (congenital, acquired, or drugs).
Potassium
- The most common cation.
- Tightly regulated.
- Affected by renal function, acid base, drugs, aldosterone.
- Hypo/hyperkalaemia is an emergency.
