3. Disorders Of Potassium Balance

Question 1

Describe the distribution of potassium around the body.

Answer 1

1. Humans: 60% water, 1.4% potassium
   - Men weigh 70kg
   - Total body water: 42L (70x60%)
2. 2/3 of total body water is intracellular
   - Intracellular potassium concentration: 140 mmol/L
   - 42 liters × ⅔ × 140 = 3,920 mmol of potassium
3. 1/3 of totally body water is extracellular
   - Extracellular potassium concentration: 4 mmol/L
   - 42 liters × ⅓ × 4 = 56 mmol of potassium

Total body potassium: 3976 mmol
Extracellular potassium: 56 mmol
Plasma potassium: 12 mmol

Question 2

How is potassium regulated in the body?

7

Answer 2

1. Intake
2. Cellular distribution: insulin, catecholamines, pH, cell turnover, osmolality
3. Renal excretion
4. Stimulating NA-K-ATPase lowers serum potassium
5. Insulin (hormone) moves glucose and K+ and phosphate into cell
6. Decrease in pH = increase in K // increase in pH = decrease in K
7. Hypertonicity causes water to flow out of cell, taking K+ with it
   —> Extracellular compartment has higher tonicity than inner cellular compartment, so water flows from intracellular to extracellular compartment

Question 3

What is normal potassium physiology (renal potassium handling)?

What is the cortical collecting duct (CCD)?

Answer 3

• Can remain in potassium balance with intakes 10-400mmol/day
• Persistent potassium disorders = failure of renal potassium handling

CCD

1. Sodium flows down chemical gradient through eNaC = increases chemical gradient
2. Generates negative charge in tubule = increased sodium delivery
3. Potassium secretion = increased Na+K+ ATPase activity decrease intracellular sodium
4. Tubule negative charge in determinant of CCD potassium secretion
5. Disruption by chloride resorption
6. Unresorable anions increase negative charge and reduce chloride

SUMMARY:
- Filtered potassium reabsorbed by proximal tubule and loop of Henle
- All potassium which is excreted in urine is secreted by CCD
1. Tubular flow
2. Aldosterone: steroid hormone activity increase activity of Na/K ATPase, eNaC, K channel
- Potassium remains regulated if distal flow and aldosterone are balanced
- Potassium disorders happen where BOTH distal flow and aldosterone are affected
Hypokalemia: aldosterone and tubular flow = increased
Hyperkalemia: aldosterone and tubular flow = decreased

Question 4

What is hypokalemia?

What are the causes?
(3)

What are the consequences?
(4)

What is the treatment?
(1)

Answer 4

Hypokalemia: potassium level < 3.5mmol/L
Moderate hypokalemia: < 3.0 mmol/L
Severe hypokalemia: < 2.5 mmol/L

CAUSES
1. Decreased oral potassium intake (rare): contributing factor in other primary aetiologies of hypokalemia, urinary potassium losses can go as low as 10mmol/day (total body potassium = 4000 mmol)

2. Intracellular Shift: cell growth, periodic paralysis, tocolytics for preterm labour, beta agonist for asthma and COPD, refeeding syndrome
3. Increased renal excretion: primary and secondary hyperaldosteronism, diuretics, vomiting, salt wasting nephropathies, hypomagnesemia, drug toxicity, unresorbable anions, RTA, polyuria

CONSEQUENCES

1. Muscle weakness / paralysis
2. ECG changes and arrhythmia
3. Urinary concentration deficit
4. Hypertension and stroke

TX
1. Give potassium (oral > IV)

Question 5

What is hyperkalemia?

What are the causes?
3

Answer 5

Hyperkalemia: potassium over 5.4mmol/L

CAUSES

• unusual to have hyperkalemia without concurrent renal failure
  1. Increased oral potassium intake: salt substitutes, TPN, enteral supplements, blood transfusions, high potassium foods, Penicilin, Dialysate

2. Extracellular shift: hyperosmality, DKA and hyperglycaemia, cell destruction, rhabdomyolysis, tumour lysis syndrome, drugs, beta blockers, Digoxin, succinylcholine, acdemia
3. Decreased renal excretion: renal failure, hypoaldsonterism, drugs (ACEi, ARB, NSAIDs, Spirnolactone, Amiloride, Trimeterene, Trimethoprim), RTA 1 + 4, Gordon’s Syndrome

Question 6

How do you lose GFR?

Answer 6

Decrease Na delivery to distal nephron preventing potassium excretion

Occurs in: kidney failure, NSAID, Gordon’s Syndrome

Question 7

How is the eNaC channel blocked?

Answer 7

1. Drugs: Trimaeterne, Amiloride, Timethoprim (abx)

2. Diseases: Type 1 RTA (electrogenic), Psuedohypoladersteronism 1

Question 8

What is hypoaldosteronism?

What are its causes?
(5)

What are the consequences?
(2)

What is the treatment? What is the goal of treatment?
(7)

Answer 8

Hypoaldosteronism: reduces number and activity of eNaC, Na/K ATPase and potassium channel

CAUSES
1.	Congenital 
2.	Adrenal insuffuciency: Addison’s Disease
3.	Diabetes: hyporenin-hypoalsosterone 
4.	Drugs:
—> ACEi / ARB / Renin Inhibitors
—> Heparin 
—> Ketoconazole 
5.	Competitive Inhibition: Spironolactone 

CONSEQUENCES
1. Muscle weakness / paralysis
2. ECG changes and arrhythmias
—> Increased extracellular potassium reduces myocardial excitability, with depression of both pacemaking and conducting tissues
—> Increasing potassium leads to suppression of the SA node and conduction by the AV node and His-Purkinje system

TX

1. Stop all sources of potassium
2. IV fluids
3. Enteral feeds
4. Parenteral nutrition
5. Dialysate
6. Antibiotics
7. Blood products

GOAL OF TX
-	Goal: prevent arrhythmia —> calcium stabilizes cardiac membranes
o	Digoxin antidote for dig toxicity  (DigFAB)
o	Albuterol
o	Insulin (IV)
o	Inhaled beta-agonists EFFECTIVE
o	Sodium bicarbonate INEFFECTIVE 
o	Diuretics
o	Fludrocortisone
o	Polystyrene resins
o	Dialysis