Term
| What is the importance of the transcellular K+ gradient and how is it maintained? |
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Definition
3-5 ECF and 120-150 ICF
1) Provides K+ ions as substrates for transport processes and determines resting membrane potential
**Hypokalemia causes hyper-polarization of membrane potential**
2) Na/K ATPase |
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Term
| Distinguish between "external" and "internal" potassium balance. |
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Definition
1) External- total body K+ though alterations to intake and excretion
2) Internal- ICF and ECF balance. |
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Term
| Describe the course of K+ handling in the nephron. |
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Definition
90% of filtered K+ is reabsorbed
1) 65% is PT (passive)
2) 25% in TAL
2) BOTH reabsorbed and secreted in the CD (tightly regulated) |
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Term
| How is K+ secreted in the collecting duct? |
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Definition
Secreted from the PRINCIPLE cell
- ROMK and ENaC in apical membrane
- Na/K ATPase in basolateral membrane
- High-resistance tight junctions between cells
Resorbed by the INTERCALATED CELL
- H+ K+ ATPase in apical membrane
- Na/K ATPase in basolateral
1) Na+ uptake into the principle through ENaC creates negative electrical PD across apical membrane that favors K+ excretion through ROMK
**Stimulated by Aldosterone**
2) K+ accumulates in tubular lumen, and is reabsorbed by the Intercalated cell, via H+/K+ ATPase. |
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Term
| How is distal tubular K+ handeling regulated? |
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Definition
Serum Aldosterone and Distal Tubular Flow Rate are of the greatest importance
1) Peritubular factors
- Serum [K+]
- Serum aldosterone (stimulates ENaC)
- extracellular pH
2) Luminal factors
- distal tubular flow rate
- DT sodium delivery
- luminal anion composition |
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Term
| How is potassium handling altered by dietary K+ intake? |
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Definition
Increased serum K+ leads to increased excretion.
1) High K+ intake increases apical membrane Na+ and K+ transport and Na/K ATPase activity
2) Acutely, K+ secretion increases (partly due to aldosterone)
3) Chronically, Potassium Adaptation occurs, and aldosterone-independent increased secretion occurs.
- Na/K ATPase activity increases
- Na+ and K+ transport increases in apical membrane
- Decreased K+ reabsorption by intercalated cells. |
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Term
| What happens to intercallated DT cells during potassium deprivation? |
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Definition
| They increase apical cell membrane area and increase potassium transporter expression (H+/ K+ ATPase) |
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Term
| How does aldosterone regulate K+ secretion in the collecting duct of the distal nephron? |
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Definition
Aldosterone stimulates secretion from principal cells by 1) AIP expression, 2) Na/K ATPase activity and 3) Apical Na and K transporter expression.
1) Aldosterone binds intracellular MR, which translocates to nucleus and leads to increased AIP translation.
2) Aldosterone increases Na+/K+ ATPase activity directly increasing K+ entry and generating Na+ gradient form apical Na+ reabsorption.
3) Increases number of apical membrane Na+ and K+ channels (generates lumen-negative electrical potential difference) |
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Term
True or False:
Aldosterone elevation leads to progressive renal potassium loss. |
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Definition
True.
Unlike sodium excretion, which exhibits "Aldosterone escape," potassium excretion is persistent despite change in intake. |
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Term
| How does extracellular pH regulate potassium handling? |
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Definition
Peritubular regulator of distal tubular K+ handling.
**Transient and limited**
H+ concentration determines gradient for H+/K+ transporter in principal cells.
1) Acidemia decrease intracellular [K+] and increases secretion
2) Alkalemia increases intracellular [K+] and decreases secretion |
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Term
| How does Distal Tubular Flow rate determine K+ handling? |
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Definition
1) Increased flow rate stimulates K+ secretion
- faster flow clears excreted potassium from lumen more quickly, allowing more to come out.
2) Decreased flow rate inhibits K+ secretion
- Secreted K+ sticks around in tubular lumen, so less is secreted. |
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Term
| How does Distal Tubular Sodium Delivery determine K+ handling? |
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Definition
Luminal factor
1) Increased sodium delivery stimulates DT sodium reabsorption, which creates the negative luminal potential that INCREASES K+ secretion
**flow rate is really always associated with increased sodium delivery** |
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Term
| How does Distal Tubular Anion Composition determine K+ handling? |
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Definition
Replacing chloride with other anions increases K+ secretion, since they are less well reabsorbed by the collecting duct.
**Adds to negative lumen PD due to Na+ reabsorption and further enhances gradient from K+ excretion** |
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Term
| What happens to K+ handling during intravascular volume depletion? |
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Definition
Serum aldosterone levels and distal tubular flow rate changes equalize each other to balance secretion.
1) Distal tubular flow rate will decrease, which decreases K+ secretion (less clearance of secreted K+ and less Na+ reabsorption).
2) Aldosterone release will increase because of RAAS system, so it will increase K+ secretion |
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Term
| How can you clinically assess renal potassium excretion? |
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Definition
1) Transtubular potassium gradient is used as index of secretion in cortical collecting duct.
Ratio of estimated K+ concentration in cortical collecting duct (CCDk) to plasma K+ concentration (Pk)
CCDk is estimated as= Uk x (Posm/Uosm)
TTKG= (Uk/Pk) / (Uosm/Posm)
During K+ depletion, TTKG is <2.5 (clearance decreases)
During K+ loading, TTKG > 10 (clearance increase) |
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Term
| How is internal K+ balance regulated on the cellular level? |
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Definition
1) K+ uptake via Na+/K+ APTase (stimulated by Insulin, Aldosterone and Catecholamines via B2)
2) K+ secretion dependent on K+ permeability |
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Term
| What 3 chemicals stimulate intracellular K+ uptake and how? |
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Definition
1) Insulin
- High splanchnic K+ concentration stimulates Pancreatic insulin release
- Insulin release stimulates Na/K ATPase in basolateral membrane.
2) Catecholamines
- Increased Na/K ATPase activity via B2 receptor in liver and muscle
3) Aldosterone
- less of an effect than on external potassium balance. |
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Term
| How do changes in serum bicarbonate concentration influence potassium handling? |
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Definition
1) Increased [HCO3-] causes K+ to shift into cells (H+ is pulled out)
2) Decreased [HCO3-) causes K+ to shift out of cells. |
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Term
| How do changes in serum pH influence internal K+ handling? |
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Definition
1) Acidosis causes EC K+ accumulation, since H+ moves in
2) Alkalemia causes IC K+ accumulation, since H+ moves out |
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Term
| How does plasma tonicity influence K+ handling? |
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Definition
- Increased plasma tonicity cause fluids to exit IC compartment and enter EC compartment.
- fluids "drag" K+ with them. |
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Term
| What happens to EC K+ during cell lysis and proliferation? |
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Definition
1) Lysis- K+ is released from dying cells rapidly (increase)
2) Proliferation- EC K+ taken up by proliferating cells (decreases) |
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Term
| What are the underlying defects in Hyperkalemic and Hypokalemic periodic paralysis disorders of skeletal muscle? |
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Definition
1) Hyperkalemic= VG Na channel defect
2) Hypokalemic= Dihydropyridine type calcium channel defect. |
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Term
True or False:
Disorders affecting external potassium balance generally produce acute disorders of hyperkalemia. |
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Definition
False.
External balance= chronic hyperkalemia
Internal balance= acute hyperkalemia |
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Term
| What major factors influence External (whole body) potassium balance potentially leading to chronic hyperkalemia? |
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Definition
Intake, Excretion, Tubular FLow, Mineral-corticoids, Tubular function
1) Excessive K+ intake
2) Decreased Renal excretion
- acute renal insufficiency
- chronic renal insufficiency (only at GFR <15-20 ml/min)
3) Decreased Distal Tubular Flow
- volume depletion
- reduced arterial blood flow (CHF, cirrhosis, nephrotic syndrome)
- Meds: NSADs via PGE inhibition and ACE- inhibitors
4) Mineralcorticoid deficiency
5) Distal tubular dysfunction (lack of response to aldosterone) |
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Term
| What major factors influence Internal potassium balance potentially leading to acute hyperkalemia? |
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Definition
1) Insulin deficiency
2) Beta-adrenergic blockage
3) Hypertonicity (hyperglycemia)
4) Acidemia (Metabolic and Hyercholoremic especially)
5) Cell lysis |
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Term
| What is "Pseuohyperkalemia"? |
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Definition
| Laboratory error indicating high EC K+ despite lack of EKG changes |
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Term
| How does Hyperkalemia manifest clinically? |
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Definition
Resting membrane potential is depolarized leading to a net reduction in membrane excitability because of inactivation of voltage-sensitive Na+ channels
1) Cardiac toxicity
2) Neuromuscular |
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Term
| How do you treat Hyperkalemia medically? |
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Definition
Serum K+ >6-6.5 meq/L or ECG manifestations
1) Acutely (Membrane potential, get K+ into cells and increase elimination)
a) IV Calcium to raise threshold potential and reduce cardiotoxicity (rapid but short duration solution)
b) IV insulin, beta-agonists and sodium bicarbonate to get K+ back into cells
c) Increase elimination with diuretics and IV saline, or with hemodialysis and GI ion exchange resins.
2) Chronically
- treat underlying process and RESTRICT INTAKE.
- enhance distal tubular sodium delivery and flow and mineralcorticoid replacement if needed. |
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Term
| How does hypokalemia due to changes in external K+ balance generally arise? |
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Definition
1) Low intake
- K+ is never fully conserved (as opposed to Na+)
- Alcoholism and Malnutrition
2) Extrarenal loss
- GI due to metabolic alkalosis (low extracellular H+ draws K+ out of cells) and secondary hyperaldosteronism.
- Cutaneous losses
3) Renal loss
- HTN (MR upregulation) or normotensive |
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Term
Why is hypokalemia often seen in the context of HTN.
What are the major Hypertensive Hypokalemic disorders? |
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Definition
HTN causes MR up-regulation, which leads to more aldosterone-dependent K+ excretion due to AIP expression and increased sodium reabsorption.
1) HyperReninemia
- renal artery stenosis or renin-secreting tumor
2) Primary hyperaldosteronism (Conn's syndrome)
- MR excess secretion from adrenal disease
3) Cushing's syndrome
- Exogenous steroid therapy
- Cortisol hypersecretion from adrenal tumor
4) Congenital adrenal hyperplasia
- Increased ACTH resulting is defects in cortisol biosynthesis. |
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Term
How can potassium loss occur in normotensive patients?
(hint: 4 ways) |
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Definition
Remember tubular acidosis OR blood alkylosis will cause K+ excretion
1) Osmotic diuresis
- Glucosuria with DM or urea from acute renal failure
2) Renal tubular acidosis (K+ exchanged form H+)
3) Vomiting or nasogastric drainage (metabolic alkalosis)
- Increased bicarbonate delivery to distal nephron and secondary hyperaldosteronism
4) Ureteral diversion
- Exchange of K+ and HCO3- for Na+ and Cl in the intestinal epithelium due to diversion of urine to illeum. |
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Term
True or False:
Tubular acidification will increase K+ excretion. |
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Definition
True! This is because the increased H+ ions in intercalated cells prevents K+ uptake
IF this was metabolic acidosis, the opposite would occur, and K+ would be retained. |
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Term
| What factors regulate internal K+ balance and cause Hypokalemia? |
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Definition
All conditions must increase K+ translocations from ECF to ICF to produce hypokalemia.
Hypokalemia involves too much K+ in cells
1) Insulin excess (stimulation of Na/K+ ATPase brings more K+ into the cell)
2) Catecholamine excess (Excess B2-mediated K+ uptake into cells)
3) Alkalemia (high serum HCO3- causes K+ to enter cells)
4) Cell proliferation (K+ taken up by rapidly dividing cells). |
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Term
| How can you treat Hypokalemia? |
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Definition
1) Potassium repletion
- Oral
- IV (WARNING because cardiac and NM effects)
2) K+ sparing diuretics
- Amiloride, Triamterene for primary renal K+ wasting
- Spironolactone for hyperaldosteronism. |
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