Potassium Homeostasis & Disorders

Potassium Distribution in the Body

Intracellular [K+]
Na+ 120-150 meq/L
Potassium distribution in body fluid 2 K+
compartments  3 Na+
 Total body K+ stores: 50-55 meq/kg K
+

body weight (3500-4000 meq K+ total)

Em = -90mV
 Extracellular fluid compartment: 2%
Extracellular [K+]
[K+] = 3.5-5.0 meq/L (50-100 meq K+) 3.5-5.0 meq/L

 Intracellular fluid compartment: 98%

[K+] = 120-150 meq/L

 Large cellular K+ (and Na+)

concentration gradients are
maintained by the Na,K-ATPase
 Potassium Gradient and Cellular Functions

Cellular functions
 Primary determinant of cell resting
membrane potential
 Substrate for membrane transport
processes
Intracellular [K+]
Na+ 120-150 meq/L

Changes in transmembrane 2 K+
potassium gradient
 Alter cell membrane resting potential
K+
K +  3 Na+

 Alter neuromuscular excitability K+ Em = -90mV

 Cardiac conduction & cardiac
pacemaker rhythmicity Extracellular [K+]
 Neuronal function 3.5-5.0 meq/L
 Vascular smooth muscle tone
 Skeletal muscle function
 Impair cell membrane transport
processes
 Extracellular Potassium Concentration and
Cell Membrane Potential

+30 Membrane potential  ln [K]o

0 [K]i

-30 Depolarization
mV Hyperpolarization
-60 Threshold

-90 Resting

-120
Normal Hypokalemia Hyperkalemia

Hypokalemia hyperpolarizes excitable tissues

Hyperkalemia depolarizes excitable tissues
 Potassium Homeostasis

The regulation of potassium homeostasis can be divided into two

main processes:
External Balance: The regulation of total body potassium content
through alterations in potassium intake (e.g. dietary) and excretion (e.g.
renal, GI)
Internal Balance: The regulation of the distribution of potassium
between intracellular fluid (ICF) and extracellular fluid (ECF)
compartments
Intake

External
Balance
Internal

K +
Balance
K+
3.5-5.0 meq/L
Extracellular Fluid (ECF)
120-150 meq/L

Excretion Intracellular Fluid (ICF)

 Hyperkalemia
Plasma [K+] > 5.0
Hyperkalemia may be the result of disturbances
in external balance (total body K+ excess) or in
internal balance (shift of K+ from intracellular to
extracellular compartments)
Hyperkalemia: Disorders of External Balance

 Renal K+ excretion

Excessive Acute & chronic

K+ intake renal failure

 Distal tubular Distal tubular

flow dysfunction

Mineralocorticoid
deficiency
Hyperkalemia: Disorders of Internal Balance

 Insulin deficiency
 2-Adrenergic blockade
 Hypertonicity
 Acidemia
 Cell lysis
 Clinical Manifestations of Hyperkalemia

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

Cardiac toxicity
 EKG changes
 Cardiac conduction defects
 Arrhythmias

Neuromuscular changes
 Ascending weakness, ileus
EKG Manifestations of Hyperkalemia

Normal
Increasing Serum K+

Peaked T-wave

Wide QRS Complex

Shortened QT Interval
Prolonged PR Interval

Further Widening of QRS Complex

Absent P-Wave

Sine-Wave Morphology
(e.g. Ventricular Tachycardia)
 Medical Treatment of Hyperkalemia

Membrane Stabilization
 IV calcium

Internal Redistribution
 IV insulin (+ glucose)
 -adrenergic agonist (albuterol inhaled)

Enhanced Elimination
 Kayexalate (sodium polystyrene sulfonate) ion exchange resin
 Loop diuretic
 Hemodialysis
 Hypokalemia
Plasma [K+] < 3.5
Hypokalemia may also result from disturbances
in external balance (total body K+ deficiency) or
internal balance (transmembrane K+ shifts)
 Hypokalemia: Disorders of External Balance

Increased Increased
Inadequate renal K+ losses
extrarenal
dietary intake + Hypertension
K+ losses
Hypokalemia: Disorders of External Balance

Inadequate K+ Intake
Malnutrition

Extrarenal Losses
Gastrointestinal losses
 Diarrhea
 Enteric fistulas

Cutaneous losses
 Burns
 Hypokalemia: Disorders of External Balance

Disorders Associated with Renal Potassium Losses

Hypertensive Disorders
 Hyperreninemia
 Renin excess (renal artery stenosis, renin-secreting tumor)

 Primary hyperaldosteronism (Conn’s Syndrome)

 Mineralocorticoid excess (adrenal hyperplasia, tumor)

 Cushing’s syndrome
 Glucocorticoid excess (exogenous, pituitary, adrenal)

 Congenital adrenal hyperplasia

 Enzymatic defects in cortisol biosynthesis (excess
aldosterone precursors)
 Hypokalemia:
Disorders of External Balance

Disorders Associated with Renal Potassium Losses

Normotensive Disorders
 Diuretics
 Osmotic diuresis
 Glucosuria

 Renal tubular acidoses

 Prolonged vomiting, nasogastric drainage
 Ureteral diversion
 Ureteroileostomy, ureterosigmoidostomy
Hypokalemia: Disorders of Internal Balance

 Insulin excess
 Catecholamine excess
 Myocardial ischemia/infarction
 Delirium tremens
 Pharmacologic agents

 Alkalemia
 Cell proliferation
 Rapidly proliferating leukemia or lymphoma
 Clinical Manifestations of Hypokalemia

Cardiac Metabolic
 EKG changes  Glucose intolerance
 Arrhythmias  Growth retardation

Smooth muscle Renal

 Hypertension  Increased renal ammoniagenesis
 Ileus  Nephrogenic diabetes insipidus

Skeletal muscle

 Weakness
 Rhabdomyolysis
 EKG
EKG Manifestations
Manifestations of
of Hypokalemia
Hypokalemia

Normal
Decreasing Serum K+

Flat T-wave

Prominent U-wave

Depressed ST-segment
Treatment of Hypokalemia

Potassium Replacement
 Oral or IV

Potassium-sparing diuretics
 ENaC sodium channel inhibitors
 Amiloride, triamterene
 Mineralocorticoid antagonists
 Spironolactone