Potassium Flashcards
Potassium Physiology and Homeostasis
Potassium Background
Total body K+ stores in adults: ~3,000 to 4,000 mEq (50 to 55 mEq/kg body weight)
Unlike Na+, 98% of K+ is intracellular. Intracellular K+ concentration is ~140 mEq/L whereas plasma K+ is ~4 to 4.5 mEq/L.
Potassium Physiology and Homeostasis
Potassium Background
The differential location of Na+ and K+ is maintained by (3)Na+- (2)K+-ATPase in cell membrane, which pumps 3 Na+ out in exchange for 2 K+ into cell (3:2 ratio).
Functions of K+
Cell metabolism (i.e., regulation of protein and glycogen synthesis)
Major determinant of resting membrane potential across cell membrane → necessary for generation of action potential required for normal neural and muscular function
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Input: blood transfusions (particularly old blood products due to extracellular K+ leakage), dietary supplements (salt substitutes [KCl], high K+-containing foods)
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Output (i.e., bodily loss): skin (sweats, extensive burns), respiratory (airway secretions), gastrointestines (large volume vomiting, nasogastric suctions, fistulas/drainages, diarrhea, renal excretion)
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants

Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants
K+ loss associated with GI fluid loss occurs via:
Direct K+ loss from vomitus/gastric fluids is relatively low—~5 to 20 mEq/L of fluid loss.
More significantly, there is renal K+ loss via associated volume depletion, compensatory hyperrenin, and hyperaldosteronism.
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants
Extracellular pH:
Low extracellular pH shifts K+ out of cells in exchange for H+ and vice versa (K+/H+exchange).
This effect is most pronounced with kidney failure–associated metabolic acidosis and less pronounced with organic acidoses (lactic acid, ketoacids), metabolic alkalosis, and respiratory acidosis/alkalosis.
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants
Extracellular osmolality: Hyperosmolality shifts water out of cells, which leads to:
Higher intracellular K+ concentration, hence more favorable gradient for K+ exit into plasma
Extracellular K+ shift due to solvent drag effect
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants
Na+-K+-ATPase:
Stimulated by insulin, aldosterone, β2-agonists (e.g., drug-induced cellular K+ uptake, thus hypokalemia: albuterol, terbutaline, dobutamine, isoproterenol)
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants
Na+-K+-ATPase:
Inhibited by α-agonists, presumably via inhibition of renin release, thus downstream hypoaldosteronism and hyperkalemia. (NOTE: α-agonists are vasoconstrictive agents such as phenylephrine and the commonly used agent norepinephrine in the critical care setting. These agents may cause hyperkalemia via their α-agonistic activity). Dopamine has weak to moderate α-1 activity and could contribute to minimal increase in S[K+] if used in high doses.
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants
ATP-dependent K+ channels: ATP depletion with exercise opens up more K+ channels →K+ leaves cells → local increase in plasma K+ enhances vasodilatation, hence blood flow and energy delivery to exercising muscles. This effect is impaired with K+ depletion.
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants
Plasma K+ concentration: Passive movement in or out of cells depends on acute plasma K+concentration changes.
Cell lysis: Cellular K+ release into plasma: tumor lysis, rhabdomyolysis, hemolysis, bowel infarction
Plasma K+ concentration (P[K+]), typically measured as serum K+ (S[K+]) and total body content depend on:
Cellular K+ Shifts:
Major Determinants
Cell production/anabolism: K+ uptake for cell production (i.e., red blood cells, platelets) with folic acid or vitamin B12 therapy for megaloblastic anemia; refeeding syndrome.
Renal Potassium Handling:
Potassium balance depends on K+ Reabsorption and Secretion

K+-reabsorption:
Proximal tubules: passive reabsorption; follows Na+ reabsorption
Thick ascending limb loop of Henle: active reabsorption via Na+-K+-2Cl
K+-reabsorption:
Cortical and outer medullary collecting ducts α-intercalated cells H+-K+-ATPase reabsorbs K+ in exchange for H+; Activity of this pump is increased with K+ depletion and reduced with K+loading and facilitated by aldosterone.
K+ secretion:
Medullary K+ recycling:
Reabsorbed medullary K+ is secreted back into the lumen at the S3 segment of late proximal tubules and descending limb loop of Henle for subsequent reabsorption at thick ascending limb loop of Henle.
Maintenance of high medullary K+ concentration is thought to minimize passive K+ back-leak
Regulated K+ secretion via the renal outer medullary potassium channel (ROMK) at the connecting and collecting tubules:
Efficiency depends on plasma K+ concentration and (1) distal Na+ delivery, (2) generation of transepithelial potential difference (negative lumen) via Na+ entry into ENaC in principal cells at aldosterone-sensitive distal nephron segment, (3) distal urine flow (to maintain the favorable electrochemical gradient for K+ secretion), (4) presence of aldosterone (regulates expression of ENaC, Na+-K+-ATPase), (5) sensitivity to aldosterone, and (6) kidney mass.
Regulated K+ secretion via the renal outer medullary potassium channel (ROMK) at the connecting and collecting tubules:
ADH is also thought to increase the number of luminal ROMK channels.
NOTE
The first response to a K+ load is intracellular uptake, a process facilitated by basal levels of catecholamines and insulin. Subsequently, the kidneys will excrete any excess K+.
Diagnosis of Potassium Disorders (Dyskalemias)
Common indices used to determine renal versus extrarenal causes of potassium disorders:

Renal Potassium Handling with Normal Renal Function
Long-term potassium homeostasis occurs primarily through changes in renal potassium excretion. Serum potassium is almost completely ionized, is not bound to plasma proteins, and is filtered efficiently by the glomerulus.
The proximal tubule reabsorbs the majority (~65% to 70%) of filtered potassium, but there is relatively little variation in proximal tubule potassium reabsorption in response to hypokalemia or hyperkalemia.
In the loop of Henle, potassium is secreted in the descending loop, at least in deep nephrons, particularly with adaptation to a large K+ intake, and is reabsorbed in the ascending loop through the action of the Na+-K+-2Cl− cotransporter.




