Potassium Balance

Question 1

Where is ROMK (renal outer medullary potassium channel) found? and what’s its function?

Answer 1

K channel that allows the K+ that is reabsorbed to be recycled back across the luminal membrane into the tubule

• K that comes out increases the lumen positivity that causes passive paracellular transport of +ve charges such as K, Ca, Na, and Mg.

Question 2

Where is K+ secreted?

Answer 2

Occurs in the principle cells of the Cortical DCT and Medullary DCT

• The K secretion is associated with Na reabsorption in the segment

Question 3

What are the Mechanistic effects of aldosterone on Potassium secretion?

Answer 3

Aldosterone => stimulates the Na/K ATPase pump to move Na out of the cells and K into cells
=> synthesis of new Na and K channel for apical membrane.
- Na passively flows in through new apical channel (due to inc pump activity)
- K then flows out (secretion) to maintain the electroneutrality

Question 4

Factors that effect K secretion in the principle cells?

Answer 4

1. concentration gradient of K across the basolateral membrane – it depends upon serum K concentration
2. electrical gradient across the luminal membrane – it depends upon the reabsorption of Na through the Na channels in the luminal membrane. Which in turn depends upon the Na concentration in the tubular lumen (distal delivery of Na)
3. K permeability of the luminal membrane - that depends upon the number of open K channel on the luminal membrane. Which is affected by the aldosterone

Question 5

What is the effect of aldosterone on K+ secretion?

Answer 5

Aldosterone => Potassium secretion

Question 6

What happens to K+ secretion on a low potassium diet?

Answer 6

Constant low level secretion

• even with inc Na delivery to distal tubule
• happens because low K will remove stimulation of aldosterone secretion.

Question 7

What happens to K+ secretion on a high potassium diet?

Answer 7

Enhanced secretion

• increases the serum K level which will increase the:
  1. K concentration gradient between intracellular and extracellular K level

2. Serum aldosterone level (“most potent stimulator” - wiki)

Question 8

In what conditions would you see decreased potassium secretion?

Answer 8

1. Renal failure
2. Distal tubule dysfunction
3. Decreased distal tubule flow
4. Hypoaldosteronism (or if it’s action is blocked

Question 9

What occurs if potassium secretion id decreased below normal?

Answer 9

K+ remains in plasma

=> hyperkalemia

Question 10

In what conditions would you see increased potassium secretion?

Answer 10

A. Increased distal Na delivery

1. Diuretics - loop and thiazides
2. Bartter’s syndrome
3. Gitelman’s syndrome

B. Hyperaldosteronism

i. ) Primary
ii. ) Secondary:
1. Vomiting and NasoGastric suction

Question 11

How is the internal K+ balance maintained?

Answer 11

by regulating the K transport across the cell membrane via:

• Na/K ATPase pump
• passive K+ outflow channels

Question 12

Factors that affect the internal balance of potassium (I.e. movement across the cell membrane)

Answer 12

1. Plasma K concentration
2. Insulin
3. Epinephrine
4. Acid-base disturbance
5. Plasma tonicity (osmolarity)
6. Cell lysis and proliferation

Question 13

How does insulin effect the movement of K across the cell membrane?

Answer 13

Insulin moves K+ INSIDE the cells, but it does not directly work on Na/K pump

• Instead, insulin stimulates a NaH exchanger on the cell membrane that moves Na+ in and H+ out
• this intracellular Na than activate the NaKATPase pump and moves K INSIDE the cells.

Question 14

How does epinephrine effect the movement of K across the cell membrane?

Answer 14

Activate the NaKATPase pump by stimulating beta receptor.
- Any other hormones or drugs that can stimulate beta receptor will stimulate NaKATPase pump.

• Examples:
  1. Albuterol (beta receptor agonists and used in bronchial asthma)
  2. Deficiency of insulin (as in diabetic patients)
  3. Beta Blockers (Na/K-ATPase pump activity will be impaired w/ decrease movement of K from ECF to ICF. But the K channel which is not affected by the hormones will remain open and will continue to move K ICF to ECF which will result in elevated K in ECF)

Question 15

How does the plasma K+ level affect movement across the cell membrane

Answer 15

Directly affects the K diffusion out of the cells

- If the serum K level is low then gradient will be high and so there will be more K coming out of the cells.

Question 16

How do changes in Acid-base level affect the internal balance of potassium?

Answer 16

Changes in extracellular pH produce reciprocal shifts in H+ and K+ between extracellular and intracellular fluid compartments.
- Metabolic acid-base disturbances > respiratory disturbances

Question 17

How do changes in plasma tonicity (osmolarity) affect the internal balance of potassium?

Answer 17

Elevated plasma osmolality or hypertonicity
=> water moving out of cells =>

1. Solvent drag (K+ gets dragged w/ water)
2. Inc. IC [K+] => inc. [K+] gradient between ECF and ICF => passive diffusion out of cells

Question 18

How does cell lysis affect the internal balance of potassium? and when does this occur?

Answer 18

Intracellular K+ is released into the extracellular space yielding an increase in extracellular [K+] (hyperkalemia)

• Rhabdomyolysis (breakdown of muscle cells)
• Hemolysis (breakdown of RBCs)

Question 19

How does cellular proliferation affect the internal balance of potassium?

Answer 19

K+ is rapidly taken up by proliferating cells => fall in extracellular potassium levels

• as seen in malignancy

Question 20

Causes of hyperkalemia?

Answer 20

1. Excessive intake
2. Decreased Renal excretion
3. Internal Redistribution (release from ICF)

Question 21

Conditions that cause hyperkalemia via decreased renal excretion?

Answer 21

1. Renal Failure (acute and chronic)
2. Distal tubule dysfunction
3. Hypoaldosteronism (primary or if it’s effect on tubule are blocked)

Question 22

Conditions that cause hyperkalemia via internal redistribution?

Answer 22

1. Insulin deficiency
2. Beta-blockers
3. Alpha receptor agonists
4. Acidosis
5. Hyperosmolarity
6. Cell lysis

Question 23

EKG changes with hyperkalemia in progressivly worsening order

Answer 23

1. Tall T wave
2. widening QRS
3. Sine wave

Question 24

Signs and symptoms of hyperkalemia

Answer 24

1. Cardio toxicity manifesting as:
   - EKG changes
   - Cardiac conduction defects
   - Arrhythmias -> bradycardia
2. Neuromuscular changes
   - Ascending weakness, and paralysis

Question 25

Tx of hyperkalemia?

Answer 25

1. Stablization of cardiac muscle - IV calcium 2. Lower K+ levels a. ) Move K+ into cells - insulin - bicarbonate - beta-agonists (albuterol) b. ) remove K+ from body - Diuretics - dialysis - cation exchange resin (kayexalate)

Question 26

Causes of hypokalemia? (serum [K+]

Answer 26

1. decreased intake 2. Internal redistribution 3. Increased renal/ GI excretion

Question 27

Normotensive diseases that cause hypokalemia?

Answer 27

1. Metabolic alkalosis (high bicarb) - Diuretics - Prolonged Vomiting, Nasogastic suction - Bartter’s syndrome, Gitelman’s syndrome 2. Metabolic acidosis (low bicarb) - Renal Tubular Acidosis (RTA) - Ureteral diversion (Uretero-ileostomy, uretero-sigmoidostomy)

Question 28

A dysfunction of which part of the nephron tubule would cause hypokalemia?

Answer 28

The proximal tubule | - primary location from K+ reabsorption

Question 29

How does vomiting cause hypokalemia?

Answer 29

- Vomiting will cause loss of fluid, H+ and Cl. - Loss of fluid will decrease ECF volume, hypotension and release of hormone Aldosterone. - Loss of H will result in elevated HCO3 level in blood (metabolic alkalosis) - less Cl delivered to the distal tubule so Na will be delivered to distal tubule with negatively charged HCO3. - Inc aldosterone in collecting tubule will cause reabsorption of Na which will increase electro negativity of the lumen resulting increased secretion of K and H.

Question 30

hypertensive disorders that cause hypokalemia?

Answer 30

1. hyperreininemia - renal artery stenosis - renin secreting tumor 2. Hyperaldosteronism (primary aka Conn's) - adrenal hyperplasia - adrenal tumor 3. Cushing syndrome - glucocorticoid excess Basically anything with excess aldosterone

Question 31

EKG changes in hypokalemia?

Answer 31

1. absence of T wave 2. prominent U-wave (wave after T- not P) 3. ST-depression

Question 32

Clinical manifestations of hypokalemia?

Answer 32

Most cases are asymptomatic, but: A. Cardiac muscle: - specific EKG changes, and arrythmias. (arrythmias with increased heart rate - tachyarrythmias) B. Chronic hypokalemia - elevated BP - associated with ADH resistance and lead to nephrogenic Diabetes Insipidis

Question 33

Tx of hypokalemia

Answer 33

1. K+ replacement - usually KCl (KPO4 if also have PO4 def.) - IV K+ should be given slowly to avoid cardiac arrest w/ rapid infusion 2. Potassium sparing diuretics

Question 34

What are the two different types of Potassium sparring diuretics? where do they work?

Answer 34

1. Aldosterone receptor antagonists - act by preventing the binding of aldosterone 2. ENa channel inhibitors - Inhibiting this channel will increase the +ve charges in the lumen, which in turn will prevent K secretion. - both work in the CD