Potassium Metabolism Flashcards
1
Q
How is potassium distributed in the body?
A
- 3-4000 mEq of K
- 98% IC (120-40 mEq/L) and 2% EC (4-5 mEq/L)
- IC K mostly in muscle, but also significant storage in liver, RBC, and bone
- American diet: about 100 mEq K -> almost 100% of that excreted through kidney (min amt via lg bowel)
- Conc maintained by external balance (dietary intake v. kidney, GI excretion) and internal balance (balance b/t IC and EC compartments; can’t measure IC K)
2
Q
Where is urinary K reabsorbed and secreted?
A
-
Reabsorbed:
1. PCT: 65% of K
2. Ascending limb of LOH: 25%
3. DCT: 10% -
Secreted:
1. Collecting duct: ONLY site for K secretion
3
Q
How is K reabsorbed in the cells in the thick ascending loop of Henle?
A
-
NK2C: electroneutral channel
1. Will not work if ROMK potassium transporter is not working
2. Helps move other charges via paracellular diffusion
4
Q
What happens to K in the principal cells in the cortical and outer medullary collecting ducts?
A
- Aldosterone stimulates Na/K ATPase, promoting movement of Na from lumen into the cell, and potassium movement out of the cell via the ROMK channel
- Aldosterone: important role in external potassium balance (Na+ reabsorption; K secretion)
5
Q
What 3 factors affect K secretion in principal cells?
A
1. Conc gradient of K across cell mem – depends on serum K concentration
2. Electrical gradient across cell mem – depends on reabsorption of Na via Na channels in luminal mem, which depends on Na conc in tubular lumen -> distal delivery of Na
- If Na not reabsorbed in earlier part of tubules, more Na delivered to CD, causing more Na reabsorption via ENAC, & K loss; if not enough distal Na delivery, impaired K secretion in CD -> need lumen to be electronegative (via Na reabsorption) to promote K secretion)
3. K permeability of luminal mem – depends on # of open K channels on luminal mem -> aldosterone
- Aldo combines w/receptor in cells and INC # of open luminal Na channels -> assoc w/INC in Na/K ATPase activity and open K channels
- Hyperaldosteronism = hypokalemia; hypoaldosteronism = hyperkalemia
6
Q
How does distal tubular flow rate affect potassium secretion? Does diet affect this?
A
-
High K diet:
1. Increased K concentration gradient (more secreted at higher flow rates; steeper slope)
2. Increased aldosterone secretion - Normal K diet: INC distal tubular flow rate = INC K+ secretion
- Low K diet: increase in distal tubular flow rate does not change secretion levels
7
Q
What 4 factors can lead to decreased renal K secretion?
A
- Renal failure
- Distal tubular dysfunction: where K+ is normally secreted
- Decreased distal tubular flow
- Hypoaldosteronism: impaired release or blocked receptor
- NOTE: b/c DEC K secretion affects serum K level, these are kidney-related factors that can INC serum K level, and even lead to hyperkalemia
8
Q
What 4 factors can lead to increased renal K secretion?
A
- Increased distal Na+ delivery:
1. Diuretics (loop, thiazides): work in more prox parts of tubule, preventing Na reabsorption
2. Bartter’s, Gitelman’s: same action as diuretics - Increased aldosterone:
1. Primary -> hyperaldosteronism
2. Secondary -> decreased IV vol, dehydration, prolonged vomiting, nasogastric suction
9
Q
How is K transported across the cell membrane?
A
- Internal K balance maintained by adjusting K trans across cell mem -> conc gradient from IC to EC responsible for passive trans of K through K channel
-
Concentration gradient of K b/t IC and EC fluid is maintained by transporting K from EC to cells against conc gradient in energy dependent manner:
1. Na-K-ATPase pump: 3 Na out, 2 K in -> main pathway to transport K into the cells
2. All factors that affect internal K balance work through Na/K ATPase pump
10
Q
What 3 factors promote K mvmt across the cell membrane? How can they be inhibited?
A
- Plasma K conc: can directly affect K diffusion out of cells
- Insulin: stimulates Na/H exchanger on cell mem, so Na into cell in exchange for H -> IC Na activates Na/K ATPase, moving K inside
- Epinephrine: stimulates beta receptor, which activates Na/K ATPase; alpha inhibits Na/K ATPase
- NOTE: in insulin deficiency (i.e., diabetic), or blocked beta receptor (i.e., beta blocker), N/K ATPase activity impaired -> DEC K from ECF to ICF, but K channel (not affected by hormones) stays open, moving ICF K to ECF = elevated K in ECF (hyperkalemia)
11
Q
What 3 factors affect the internal balance of K?
A
- Acid-base disturbance
- Plasma tonicity
- Cell lysis and proliferation
12
Q
How might acid-base disturbances affect the internal distribution of K?
A
- Changes in EC pH produce reciprocal shifts in H+ and K+ between EC and IC fluid compartments
- Acidosis: K+ out, H+ in -> assoc w/hyperkalemia
- Alkalosis: K+ in, H+ out -> assoc w/hypokalemia
13
Q
By what 2 mechanisms does plasma tonicity (osmolality) affect the internal balance of K?
A
- INC plasma osmolality, hypertonicity: hypertonic ECF will cause mvmt of ICF water to ECF -> when water moves out of cell, it drags K out with it – called solvent drag (Ex: hypernatremia or hyperglycemia)
- Increased IC K conc: with ECF hypertonicity b/c H2O movement out of cells increases concentration gradient of K between ICF and ECF, resulting in more K diffusion out of cells through K channel
- Both of these will result in hyperkalemia
- Happens in diabetic ketoacidosis or diabetic hyper-osmolor state, where ECF tonicity is increased due to elevated glucose concentration
14
Q
How do cell lysis and proliferation affect the internal K balance?
A
-
Cell lysis: IC K+ released into EC space, yielding an increase in EC [K+]
1. Muscle injury – Rhabdomyolysis
2. RBC injury – Hemolysis - Rapid cellular proliferation: K+ rapidly taken up by proliferating cells, causing EC K to fall -> rare, but can happen
15
Q
What are 3 broad categorical causes of hyperkalemia? Provide some examples of each.
A
- Excessive K+ intake: oral or parenteral intake -> very rare, as long as the kidney is functioning well
- Decreased renal excretion: acute or chronic renal failure, decreased distal tubular flow, distal tubule dysfunction, hypoaldosteronism
- Internal redistribution: K released from the cell, i.e., insulin deficiency, B-2 adrenergic blockade, cell lysis, acidemia, hypertonicity
16
Q
What are the EKG manifestations of hyperkalemia?
A
- Main reason we worry about potassium is due to its effect on cardiac myocytes
- Can lead to: peaked T-wave, wide QRS, absent P-wave, and even vtach
18
Q
What is the treatment for hyperkalemia?
A
- Stabilization of cardiac muscle cells: IV calcium
-
Lowering of serum K+:
1. Moving K+ inside the cells, out of ECF: insulin (Na-H exchanger), β agonists (albuterol -> beta-2), bicarbonate (not very clear how this works, but probably similar mech to insulin)
2. Moving K+ outside the body: diuretics, cation exchange resins (kayexalate), dialysis
19
Q
Describe the various txs for hyperkalemia in terms of MOA, onset, duration.
A
- GIVE CALCIUM FIRST, esp. if any cardiac symptoms
- Insulin, bicarbonate, albuterol: moves potassium IC (these next)
- Furosemide, resin: moves K+ outside body (resin would probably be last thing you give due to delayed onset and long action)
- Dialysis: usually takes a little longer to happen (4-6 hours)
21
Q
What 2 normotensive disorders result in hypokalemia via renal losses?
A
-
Metabolic alkalosis (high HCO3):
1. NK2C inhibition: loop diuretics, Bartter’s syn
2. Prolonged vomiting, nasogastric suction
3. INH NaCl transporter: Gitelman’s syndrome, thiazides (INC distal Na+, like NK2C above) -
Metabolic Acidosis (low HCO3):
1. Renal tubular acidosis (RTA): dysfunction of renal tubules that also causes HTN (T1: INC K+ secretion in CD; T2: can’t reabsorb HCO3 or K+ in proximal tubule)
2. Ureteral diversion: uretero-ileostomy, uretero-sigmoidostomy
22
Q
How does persistent nausea/vomiting INC renal loss of potassium? KNOW THIS.
A
- Loss of fluid and HCl
- Loss of fluid + inability to intake decreases ECFV, so hypotension + release of aldosterone -> reabsorption of Na increases electronegativity of lumen, resulting in increased secretion of K and H
- Loss of H = elevated HCO3 in blood = metabolic alkalosis
- Normally in distal tubule Na, Cl reabsorbed together to maintain electroneutality of tubule, so when Cl lost, less Cl delivered to distal tubule -> instead Na delivered to distal tubule with (-) HCO3
- Hypokalemia, metabolic alkalosis in blood but aciduria in urine -> paradoxical aciduria
23
Q
What 4 hypertensive disorders can cause hypokalemia?
A
- Diuretics + these 2 syndromes cause hypokalemia by increasing distal Na delivery.
1. Hyperreninemia (high renin): renal artery stenosis, or renin-secreting tumor
2. Primary hyperaldosteronism (Conn’s syn): adrenal hyperplasia, adrenal tumor - Cushing’s syndrome: glucocorticoid (similar to aldosterone) excess (exogenous -> more common, i.e., pt. with COPD taking steroids, pituitary, adrenal)
- Congenital adrenal hyperplasia: enzymatic defects in cortisol biosyn (excess aldosterone precursors)
24
Q
What are the EKG manifestations of hypokalemia?
A
-
26
Q
What is the treatment for hypokalemia?
A
-
Potassium replacement: usually as KCl, KPO4
1. Serum K from 4.0 to 3.0 mEq/L => deficiency of 200 to 400 mEq of potassium
2. Oral replacement: Kcl tab 20, 40 mEq
3. IV replacement: Kcl 10 mEq mixed with IV fluid over 2 hrs (if you do this too quickly, you can cause cardiac arrhythmia) -
Potassium Sparing diuretics usually used in cases of chronic hypokalemia -> 2 different types, both of which work on the CD and decrease K secretion:
1. ENAC sodium channel inhibitors (Amiloride, Triamterene): Inhibiting this channel will INC the +ve charges in lumen, preventing K secretion
2. Mineralocorticoid antagonists (Eplerenone, Spironolactone): act by preventing binding of aldo w/aldo receptors
