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
17
Q
What are the signs and symptoms of hyperkalemia?
A
- Cardiac toxicity: 1) EKG changes, 2) cardiac conduction defects, 3) bradyarrhythmias, 4) affects nerve conduction and muscle contraction
- Neuromuscular changes: ascending weakness, ileus (disruption of normal propulsion in GI tract)
- Low potassium will have similar effect on muscles and nerves
- Clinical manifestations result primarily from the depolarization of resting cell membrane potential in myocytes and neurons -> prolonged depolarization decreases membrane Na+ permeability through the inactivation of voltage-sensitive Na+ channels, producing a reduction in membrane excitability
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)
20
Q
What are 3 causes of hypokalemia?
A
- DEC K intake
- INC renal or GI excretion: GI, renal, cutaneous losses
- Internal redistribution: insulin excess, acidemia, catecholamine excess, cell proliferation
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
-
25
What are the clinical manifestations of hypokalemia?
- Chronic hypokalemia = asymptomatic
- _Cardiac_: EKG changes, tachyarrhythmias
- _Smooth muscle_: hypertension, muscle paralysis in some cases, ileus
- _Skeletal muscle_: weakness, rhabdomyolysis
- _Renal_: nephrogenic diabetes insipidus (chronic hypokalemia can cause this)
26
What is the treatment for hypokalemia?
- **_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
27
What are the important determinants of K+ secretion?
Serum Aldosterone level, distal sodium delivery
28
Can high or low serum potassium levels result in serious cardiac rhythm anomalies?
Both low and high serum potassium levels can result in serious cardiac rhythm abnormalities
