J de Zoysa: Renal Physiology; Potassium and Magnesium

Question 1

Key roles of the the Kidneys

Answer 1

1. ) Elimination of waste products
2. ) Control of fluid balance

3.) Control of minerals: K+ and Mg2+

4. ) Regulate acid-base balance
5. ) Produce hormones

Question 2

What is Magnesium and how much

Answer 2

• Is an essential cation vital for numerous physiological functions.​
• The total magnesium content of the human body is ~20 mmol/kg of fat-free tissue.
  
  • ​​~1000mmol in average man
• Highly soluble and found in high contents in the ocean

Question 3

What’s the distribution of Mg in the human body

Answer 3

• 99% of Mg is found in bone, muscle and soft tissue.
  
  • helps form the structure of the bone, hard to get at
  • Decreases with age
• Intracellular Mg concentrations range from 5 to 20 mmol/L
• Extracellular Mg accounts for 1% (0.7-1mmol/L)
  
  • some protein bound, some ionised, important for enzyme function

Question 4

Physiological purpose of Magnesium?

Answer 4

• Bone formation
• Co-factor in > 300 enzymatic reactions.
• ATP metabolism, (key enzyme)
• Muscle contraction and relaxation,
• Normal neurological function
• Release of neurotransmitters
• Regulation of vascular tone
• Cardiac rhythm
• Platelet-activated thrombosis

Question 5

Magnesium is highly soluble, what does that mean?

Answer 5

It binds a large amount of water molecules very easily, which increase its diameter and makes it hard to move through intracellular channels. Needs to be actively stripped from water molecules to move through IC

Question 6

Describe magnesium homeostasis.

Answer 6

• Mostly sourced from diet
  
  • 300mg from diet needed, some of this is from water (low amounts in NZ)
  • cereals, nuts, green leafy veges great sources
• Absorbed in the GI tract
• Kidney has a key role in regulation

Question 7

How are the kidneys important to Magnesium?

Answer 7

• Serum Mg is controlled by its excretion in the urine.
• ~2400 mg of Mg is filtered by the glomeruli.
• ~95% is immediately reabsorbed
  
  • 10-20% PCT
  • 60-70% Thick ascending limb
  • 10% DCT
• ~100 mg (5%) is excreted in the urine

Question 8

Proximal convoluted tubule Magnesium reabsorbtion ?

Answer 8

• Mechanism unsure (10-20% reabsorbed)
• speculated that the Na/K ATPase could drag it through when pulling water across

Question 9

Thick ascending limb reabsorption of Magnesium?

Answer 9

The primary place of reabsorption

• Lots of water is reabsorbed in the descending limb, which concentrates the electrolyte concentration, so K+ and Mg++ is high by the time it reaches the ascending limb
• Most important are the paracellular channels (formed by chlordane 16 and Chlordane 19) which are vital for magnesium reabsorb
  
  • those with mutations in this paracellular channel develop hypomagnesia with a low conc of magnesium in the blood, and can develop issues with this
• Other channels: Na/K transport channels, K channels that impact Mg reabsorption
  
  • arters syndrome; hypermagnesemia
    *

Question 10

Reabsorption of Mg in the DCT?

Answer 10

• transient receptor potential channels important
• Mutations can occur here → hyper magnesic → hyper calcaemic → chance of developing kidney stones

Question 11

How do we assess Mg?

Answer 11

• Serum Mg: most common, tightly regulated (0.7-1), sometimes not a good measure of bone stores
• Red cell Mg: if low they may need Mg
• 24 hour excretion: will tell us if there’s renal loss occuring (happens more over night)
• Mg retention test : give them an oral load, if it doesn’t rise then there’s an absorbtion issue
• Isotope analysis: to see distribution of Mg

Question 12

Causes of Hypomagnesamia

Answer 12

1. Decreased dietary intake
2. GI malabsorption and loss
3. Endocrine – hyperaldosteronism, DM, SIADH, “hungry bone” syndrome
4. Renal loss
   
   • • Congenital

• Acquired: eg; Drug-induced

Question 13

Drugs that can cause acquired Hypomagnesia?

Answer 13

• Aminoglycosides

• Amphotericin B

• CNI
• Cisplatin
• Cetuximab

• Omeprazole: Protein pump inhibitor, now more commonly used

• Pentamidine
• Foscarnet

Question 14

Symptoms of Hypomagnesaemia are?

Answer 14

• Weakness and fatigue

In severe cases:

• Fasciculations /cramps
• Tetany/carpopedal spasm
• Numbness paresthesiae
• Seizures
• Arrhythmias

although it’s uncommon in the community this is common in the hospital setting due to diet, drugs

Question 15

How do you treat hypomagnesemia

Answer 15

• IV magnesium (MgS)
• Oral is used in most cases

Question 16

When does hypermagnesaemia occur?

Answer 16

Usually very rare!

• In advanced CKD the compensatory mechanisms start to become inadequate and hypermagnesaemia may develop. (but usually these patient have problems with anorexia so this doesn’t occur often)

• Excessive oral administration of magnesium salts or magnesium-containing drugs: lots of reflux medication.

• Iatrogenic: resp depression, seizures, arrhythmias

Question 17

What is Potassium

Answer 17

• Potassium is the most abundant cation in the intracellular fluid.
• Maintaining the proper distribution of potassium across the cell membrane is critical for normal cell function.

Question 18

What are our Potassium levels?

Answer 18

• Adult contains ~3500mmol K+

• 300mmol in skeleton,
• 80mmol in ECF,
• Majority 90% in cells (IC) (2700mmol in muscle cells)

Question 19

Potassium homeostasis

Answer 19

Daily oral intake 1560-5850mg/day (pregnant/lactating women need more)

At healthy steady state: 90 – 95% excreted in urine

5 – 10% excreted in faeces

Question 20

Internal balance of Potassium is maintained by? How?

Answer 20

• The kidney is primarily responsible for maintaining total body K.
• Initial changes in extracellular K are initially buffered by movement of K into or out of skeletal muscle regulated by insulin and catecholamines.

Short term: buffered by K+ moving in/out of cells

Long term: buffered by the kidneys

Question 21

Tonicity and pH can affect K+ how?

Answer 21

Tonicity: Hyperglycaemia will lead to K efflux from the cell. Patients who present with TKA will often have a high initial K

pH:

• Acidosis can also drive K efflux. (to balance unbound H+)
• Alkalosis will leave to K influx. (to balance bound H+)

Question 22

Whats the overview of K+ reabsorption

Answer 22

• Freely filtered at the glomerulus
• 60-70% at PCT
• 30% at Thick ascending limb
• DCT and collecting ducts have a huge amount of control

Question 23

K+ reabsorption in the PCT

Answer 23

• paracellular mechanism driving reabsorbtion
• Na/K+ ATP ase drives K+ intracellularly, which causes paracellular movement of K+ into the blood from the lumen

Question 24

K+ reabsorption in the Thick ascending limb

Answer 24

• Active reabsorption of K+ via a Na/K/ClCl channel and the ROMK channel, and the Na/K ATPase pump

Question 25

But lots of regulation occurs at the DCT via hormones such as : **Aldosterone (and angiotensin)** How

Answer 25

* when we have a K+ load, we get an increase in plasma K+, and aldosterone is stimulated * Alternatively, if there's a reduction in the EC vol or a reduction in salt, this will drive renin → angiotensin and AT II → aldosterone production

Question 26

What affects Serum K+ levels?

Answer 26

* K+ intake (diet) * K+ losses * K redistributed from ECF in/out of cells

Question 27

Hypokaelaemia is defined as? What are the symptoms

Answer 27

* Serum K \< 3.5mmol/L * Symptoms: * Muscle Weakness * Paralysis (severe cases) * Cardiac Conduction Abnormalities * Cramps * Constipation

Question 28

What is Hyperkalaemic Periodic Paralysis

Answer 28

• Autosomal dominant (rare) or thyrotoxic **• Abnormal K+ channels** on cell membrane * Trigger is often **high carb meal ( as this produces insulin)** or **SNS activation** (b-agonist) eg. Anxiety or exercise * Excessive movement of K+ into cells * leads to **extreme weakness**

Question 29

Where can you get K+ **losses** via Renal routes which cause **Hypokalaemia**

Answer 29

• RENAL * Hyperaldosteronism: adrenal aldosterone-secreting tumor (Conns Syndrome) which overrides the usual regulation. * present with hypokalemia and hypertension * Licorice produces an enzyme that has an aldosterone-like effect an cause K+ stimulation * Diuretics affects both Na and K+ excretion. Drugs acting on the PCT the most common cause * Renal Tubular Acidosis

Question 30

Where can you get K+ **losses** via **Gut** routes which cause **Hypokalaemia?**

Answer 30

* • K losses from Faeces or Vomit * Ileostomy: hypokalaemia * Diarrhoea * Bowel Fistulae * Vomiting * NG Tube Losses

Question 31

Treatment of **hypokalaemia**?

Answer 31

* Treat the underlying problem (reason for loss) * For mild hypokalaemia (oral supplementation) * For severe use IV replacement

Question 32

Hyperkalaemia is? What are the symptoms?

Answer 32

* Defined by a K **\> 5.0mmol/L** Symptoms: * Fatigue or weakness: end stage renal disease * Paraesthesia * Nausea or vomiting * Dyspnoea * Palpitations

Question 33

How do you get Pseudo-hyperkalaemia

Answer 33

* When lab tests are left sitting, the blood cells haemolyse and the K is released from its high conc intracellular storage * ask them if they have symptoms of hyperkalaemia (fatigue/weakness), if not do a fast repeat test

Question 34

Cause of Hyperkalaemia

Answer 34

* Increased Intake: usually only an issue with those with CKD (stage 4-5) then they are unable to manage the load. Usually normal people are fine * Disruption of cell intake: * Beta blockers (block β agonist effect) * Acidosis: H+ high moving IC and Pushing K out * Rhabdomyolysis: large breakdown of cells that cause K+ release * Decreased Excretion: * Renal Failure * Hypoaldosteronism * ACEi/ARB: drugs that cause this * Other Drugs:

Question 35

What is Addisons disease? opposite of conns

Answer 35

* **Deficient secretion of aldosterone, cortisol** adrenal gland not functioning * Characteristic hyperpigmented/*tanned*: appearance due to excessive ACTH excretion * stimulating melanocytes * Symptoms: lethargy, weakness, * weight loss, low BP (excrete salt and water) Lab tests: for hyperkalaemia and hyponatraemia Diagnosis: Short synacthen test Scans Treatment: Dexamethasone, fludrocortisone

Question 36

Why should we be worried about hyperkalaemia. How do we treat it?

Answer 36

Because it can be an emergency. K+ is a huge regulator of cardiac contractility, so can get a widening of the AP, leading to eventual VF Treatment of this: * Short term: Stabilise AP * Using Intravenous Calcium → Push K into cells * This normalises membrane excitatbility * Med-long term: Reduce K absorbtion: * **'Calcium** **Resonim****'****:** gets into GI tract, bings to K in gut (increasing faecal elimination) swapping it for calcium. Can be given orally or rectally, takes 4-6hrs.

Question 37

How do B-agonists treat Hyperkalaemia

Answer 37

* Ventolin nebulisers * 5mg salbutamol * can do hourly * reduces K by 0.9-1.5mmol/L * Takes ~1/2 to 1 hour to acts, lasts 4-6 hours

Question 38

Insulin as a treatment of hyperkalaemia

Answer 38

* Insulin (SA, 10 units) + **Dextrose (50ml 50%)** * done w dex. as insulin alone will drop glucose!! * Works in 10-20mins, peaks at 30-60mins * Duration 4-6ht

Question 39

Metabolic acidosis can also cause hyperkalaemia. How do we treat the MA?

Answer 39

* Oral Bicarbonate tablets 840mg 2-3 bd/tds * In emergency; IV Bicarb 8.4% 50mL over 2 hours and repeat

Question 40

We can increase elimination via

Answer 40

* K losing diuretic * Dialysis: or a rhabdomyolsis