Potassium Homeostasis Flashcards
potassium - roles in cell functions
*creating a potential difference across cell membranes
*critical importance in the function of many cells
*our body has developed mechanisms to manage serum K+:
-regulate total body K+ content
-maintain K+ in proper distributions
importance of potassium gradient
*resting membrane potential is maintained by this potassium gradient
*increased or decreased K+ can result in fatal cardiac arrhythmias/EKG changes, muscle weakness, or even paralysis
potassium distribution
*HIGH INTRACELLULAR potassium concentration (140-150 mEq/L)
*low extracellular potassium concentration (3.5-5.5 mEq/L)
effect of hypokalemia on resting membrane potential
*hypokalemia (low serum K+ levels) → more negative resting membrane potential (hyperpolarizes cell)
*more is needed to reach an action potential
ex: when serum K+ changes from 5 mEq/L (normal) to 2.5 mEq/L, resting membrane potential changes from -90 (normal) → -108
effect of hyperkalemia on resting membrane potential
*hyperkalemia (high serum potassium levels) → more positive resting membrane potential (depolarizes cell)
*less is needed to reach an action potential
ex: when serum K+ changes from 5 mEq/L (normal) to 7.5 mEq/L, resting membrane potential changes from -90 (normal) → -79
regulation of K+ homeostasis
- cellular distribution
- renal excretion
- GI excretion
note - the KIDNEYS are primarily responsible for maintaining total body K+ content (potassium in = potassium out)
internal balance of K+
*immediate buffering of extracellular K+ into and out of skeletal muscle
*skeletal muscle serves as a reservoir to limit the fall of extracellular K+ in certain pathologic conditions
*factors mediating cellular shifts of K+:
1. insulin
2. catacholamines
3. acid-base status
4. plasma tonicity
effects of INSULIN on extracellular K+ (simple)
*insulin shifts K+ INTO CELL by inserting or activating Na+/K+ ATPase pumps
*leads to decreased serum potassium
effects of INSULIN on extracellular K+ (detailed)
- insulin binds its receptor
- binding → phosphorylation of IRS-1
- IRS-1 binds PI3-K
- IRS-1/PI3-K complex activates PDK1
- two different outcomes:
a. activates Akt- pathway to INSERT GLUT4
OR
b. activates aPKC to INSERT Na+/K+ ATPase pumps (→ insulin shifts K+ into cells)
effects of CATECHOLAMINES on extracellular K+ (simple)
*beta2 stimulation shifts K+ INTO cells
*results in decreased serum potassium
effects of CATECHOLAMINES on extracellular K+ (detailed)
beta2 stimulation → increases Na+/K+ ATPase pump ACTIVITY via cAMP and PKA-dependent pathway → shifts K+ into cells
effects of INORGANIC ACIDS on extracellular K+ (simple)
mineral acidosis (inorganic acids) shifts K+ OUT OF CELLS
effects of inorganic acids on extracellular K+ (detailed) - 2 mechanisms
- mineral acidosis decreases pH → decreases rate of NHE1 and NBCe → decreases intracellular Na+ → decreases Na+/K+ ATPase activity → NET CELLULAR LOSS OF K+
- fall in extracellular HCO3- → increases Cl- influx by Cl-HCO3- exchanger → enhances K-Cl transporter → INCREASES K+ EFFLUX
effects of ORGANIC ACIDS on extracellular K+
organic acids have NO EFFECT ON EXTRACELLULAR K+
effects of PLASMA TONICITY on extracellular K+
increased tonicity (hyperosmolarity) → increased H2O movement OUT OF CELLS → H2O movement favors K+ efflux via solvent drag → cell shrinkage leading to increased intracellular K+ → creation of a concentration gradient for K+ efflux
factors that drive K+ INTO cells
- insulin
- beta 2 stimulation (catecholamines)
- alkalosis
factors that drive K+ OUT OF cells
- insulin deficiency
- beta-ANTAGONISTS
- acidosis
- hyperosmolarity
- cell lysis
- severe exercise
- digitalis
handling of potassium in the PROXIMAL TUBULE
*bulk of K+ is reabsorbed in proximal tubule
*very little regulation occurs in response to diet
*2 mechanisms of K+ reabsorption:
1. PASSIVE PARACELLULAR REABSORPTION (primary):
-active Na reabsorption drives net fluid reabsorption in PT cells
-K+ reabsorption through SOLVENT DRAG
-proportional to Na+ and H2O
2. paracellular pathway:
-luminal voltage shifts from slightly negative to slightly positive
-ADDS FURTHER DRIVE for K+ reabsorption in distal part of proximal tubules
potassium handling in the THICK ASCENDING LOOP OF HENLE
*2 mechanisms of K+ reabsorption:
1. transcellular (primary):
-Na+/K+ ATPase maintains a low intracellular [Na+], which provides favorable drive for the NKCC cotransporter
-apical ROMK channel provides pathway for K+ to recycle from cell to lumen to provide adequate supply to sustain NKCC cotransporter
2. paracellular:
-movement through ROMK provides the slightly positive lumen needed for paracellular K+ reabsorption
note - absorption can be reversed if given loop diuretic or high K+ load
potassium handling in early DISTAL TUBULE
*K+ SECRETION begins in DT and progressively increases into CCD
*SECRETION OF K+ occurs via:
1. ROMK
2. electroneural K+/Cl- cotransporter
potassium handling in the PRINCIPAL CELLS of the CCD
*primarily responsible for K+ SECRETION
factors regulating K+ secretion
- distal delivery of Na+
- luminal flow rate
- aldosterone presence
- extracellular [K+]
effects of distal Na+ delivery on K+ secretion
*increased distal delivery of Na+ → K+ SECRETION
-diuretics, volume expansion, high Na+ diet
*decreased distal delivery of Na+ → LESS K+ secretion
-prerenal states, obstruction, low Na+ diets
*ENaC inhibitors → LESS K+ secretion
effects of tubular flow rate on K+ secretion
*increased flow rate → decreased luminal [K+] → K+ SECRETION
*low flow states (i.e prerenal states/obstruction) → LESS K+ secretion
effects of aldosterone on K+ secretion
*aldosterone → INCREASED K+ SECRETION
aldosterone → increases Na+/K+ ATPase expression/activity → increases ENaC expression/activity → activates ROMK channels → K+ secretion
effects of extracellular [K+] on K+ secretion
increased serum (extracellular) K+ concentration → directly stimulates aldosterone → INCREASED K+ SECRETION
potassium handling in the INTERCALATED CELLS of the CCD
*primarily responsible for K+ REABSORPTION via active H+/K+ ATPase
clinical manifestations of hypokalemia
*symptoms tend to be proportionate to the degree & duration of hypokalemia
1. cardiac arrhythmias (very interpatient dependent)
2. muscle weakness
3. renal manifestations
4. hyperglycemia
EKG findings of hypokalemia
*slightly prolonged PR interval
*slightly peaked P wave
*ST depression
*shallow T wave
*PROMINENT U WAVE
causes of hypokalemia
*poor intake (not really a problem)
*pseudohypokalemia (AML patients)
*shifts - hyperinsulinemic, beta agonists, alkalosis
*excess excretion:
1. excess renal excretion - drugs, hormones, mag depletion, kidney issues (increased RAAS activation → increaased excretion of K+)
2. excess non-renal excretion - skin excretion, GI excretion (diarrhea, vomiting, etc)
clinical manifestations of hyperkalemia
*muscle weakness or even paralysis
*cardiac manifestations:
-EKG changes
-conduction abnormalities/arrhythmias (RBBB, LBBB, sinus brady, VT, VF, etc)
EKG findings of hyperkalemia
*TALL, PEAKED T WAVES
*shorted QT interval
*widening of QRS complex
*loss of P → sine wave
causes of hyperkalemia
*excessive intake - dietary, K+ supplements, salt substitutes
*pseudohyperkalemia - traumatic venipuncture, CLL, thrombocytosis
*shifts - metabolic acidosis, insulin deficiency, beta blockers, digoxin overdose, cell lysis, exercise, hyperosmolarity
*decreased excretion - renal impairment, drugs/conditions that affect RAAS cascade
