Dr. Sanela REDZEPAGIC Renal Advanced trainee, discussion+Dr...Dr. Sanela REDZEPAGIC Renal Advanced...

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  • Dr. Sanela REDZEPAGIC

    Renal Advanced trainee, RPAH/Concord hosp.

    Feb 2012

  • 1. Physiology of Potassium metabolism and potassium distribution

    2. Renal potassium handling with normal renal function and CKD

    3. Potassium shifts

    4. Hypokalaemia clinical picture

    5. Diagnostic investigation

    6. Treatment

  • Potassium essential for many cellular functions

    present in most foods

    excreted primarily by the kidney

    Western diet K content~approx.70 -150 mmol

    The gastrointestinal tract efficiently absorbs potassium, and dietary potassium intake varies greatly with the composition of the diet.

  • Potassium absorption from the GIT major intracellular cation only about 2% of total body K extracell. K is a major determinant of intracellular Osmolality. Most intracellular K is contained within muscle cells.

    Total body K is roughly proportional to lean body mass. An average 70-kg adult has about 3000 to 3500 mmol.

    The ratio between ICF and ECF K concentrations strongly influences cell membrane polarization, which in turn influences important cell processes, such as the conduction of nerve impulses and muscle (including myocardial) cell contraction.

    Even small alterations in serum K concentration can have

    significant clinical manifestations.

  • This asymmetric potassium distribution between ICF and ECF compartments strongly depends upon the effects of the electrogenic sodium pump, Na+,K+-ATPase that achieves by active uptake, which occurs in virtually all cells. Na+,K+-ATPase transports two potassium ions into cells in

    exchange for extrusion of three sodium ions high intracellular potassium &low intracellular sodium activity

    Long-term potassium homeostasis is accomplished primarily through changes in renal potassium excretion via collecting duct potassium transport. Serum potassium is filtered efficiently by the glomerulus.

    Potassium reabsorption, which decreases renal potassium excretion, occurs through the action of the active potassium-reabsorbing transporter H+,K+ ATPase.

    Normal maintenance of this ratio and membrane potential is critical for normal nerve conduction and muscle contraction.

  • The major factors regulating H+,K+-ATPase expression and activity are:

    1. Potassium balance Potassium depletion increases H+,K+-ATPase expression

    increased active potassium reabsorption and decreased potassium excretion.

    2. Aldosterone increases H+,K+-ATPase expression and activity decreasing net potassium excretion, serve as a counterbalancing factor to minimize the hypokalaemia that results generally from increased aldosterone.

    3. Acid-base status

    Metabolic acidosis has both direct and indirect (mediated through alterations of ammonia metabolism) effects that increase H+,K+-ATPase potassium transport. In some cases, this may contribute to the hyperkalemia that can occur with metabolic acidosis.

  • Aldosterone lowers serum potassium concentration by two major mechanisms. stimulates potassium movement into cells (redistribution),

    and increases potassium excretion in the kidney and, to a lesser

    extent, in the gut.

    The primary renal action of aldosterone is to stimulate sodium reabsorption; but with ample sodium delivery to the late distal nephron and collecting duct, this promotes enhanced flow-dependent potassium excretion.

    Aldosterone has many effects that increase principal cell potassium secretion. These include increases in Na+,K+-ATPase expression and increased apical expression of the sodium channel ENaC. The net effect is increased potassium secretion.

  • The proximal tubule reabsorbs the majority (~65% to 70%) of filtered potassium. Very little regulation occurs in response to changes in dietary potassium intake.

    Potassium is secreted by the descending loop of Henle, at least in deep nephrons, and is reabsorbed by the ascending loop of Henle through the action of the Na+-K+-2Cl cotransporter (Fig. 9.5A). This results in modest net potassium reabsorption in the loop of Henle.

    This absorption can be reversed to secretion, however, by administration of a loop diuretic or by substantial potassium loading. Nevertheless, the majority of potassium excretion is regulated normally through active secretion and absorption in the distal tubule and collecting duct.


  • Collecting duct potassium transport occurs through distinct cell types that allow fine control of renal potassium excretion.

    The principal cell of the cortical collecting duct secretes potassium (Fig. 9.5B). Sodium reabsorption through the apical sodium channel (ENaC) stimulates basolateral Na+,K+-ATPase, and the active turnover of this pump maintains high intracellular potassium concentrations.

    Subsequent to basolateral potassium uptake, potassium is secreted into the luminal fluid by apical potassium channels and KCl cotransporters. Intercalated cells reabsorb potassium through an apical H+,K+-ATPase (Fig. 9.5C).This protein actively secretes H+ into the luminal fluid in exchange for potassium, resulting in potassium reabsorption.

    The presence of two separate potassium transport processes, secretion by principal cells and reabsorption by intercalated cells, enables effective regulation of renal potassium excretion.


  • Potassium homeostasis is relatively well preserved until glomerular filtration rate (GFR) is reduced substantially.

    Patients with chronic kidney disease (CKD) have more difficulty handling an acute potassium load. decreased nephron number

    Patients with CKD are also routinely treated with medications that alter renal potassium handling, decrease renal potassium sensitivity and result in higher serum potassium concentrations. ACE inhibitors ARBs -adrenergic receptor blockers.

  • Insulin moves K into cells via effect on the Na+,K+-ATPase pump through a mechanism separate from its stimulation of glucose entry. High concentrations of insulin lower serum K Low concentrations of insulin (in DKA) cause K to move out

    of cells, thus raising serum K, sometimes even in the presence of total body K deficiency.

    -Adrenergic agonists, especially selective 2-agonists, move K into cells - 2-Adrenergic receptor activation increases intracellular cyclic adenosine monophosphate production, which stimulates Na+,K+-ATPasemediated potassium uptake.

    Whereas -blockade and -agonists promote movement of K out of cells.

  • Acute metabolic acidosis causes K to move out of cells, whereas acute metabolic alkalosis causes K to move into cells.

    However, changes in serum HCO3 concentration may be more important than changes in pH; acidosis caused by accumulation of mineral acids (nonanion gap, hyperchloremic acidosis) is more likely to elevate serum K.

    In contrast, metabolic acidosis due to accumulation of organic acids (increased anion gap acidosis) is not associated with hyperkalemia. Thus, the hyperkalemia common in diabetic ketoacidosis results more from insulin deficiency than from acidosis.

    Acute respiratory acidosis and alkalosis affect serum K concentration less than metabolic acidosis and alkalosis. Nonetheless, serum K concentration should always be interpreted in the context of the serum pH (and HCO3 concentration).

  • Hyperosmolality, if it is due to effective osmoles, can induce potassium shifts out of cells and result in hyperkalemia.

    The proposed mechanism is that increased plasma osmolality induces water movement out of the cells, which decreases cell volume and increases intracellular potassium concentrations. This is then thought to result in feedback inhibition of Na+,K+-ATPase, shifting potassium from the intracellular to the extracellular compartment and normalizing intracellular potassium concentration.

    Both glucose, in a patient with intact insulin secretion, and urea are ineffective osmoles because they rapidly cross plasma membranes and therefore do not alter cell volume.

    Importantly, hyperglycemia in a nondiabetic patient, if it stimulates endogenous insulin secretion or if exogenous insulin is given, can cause insulin-induced cellular potassium uptake and resultant hypokalemia.

  • Exercise hyperkalemia due to -adrenergic receptor activation that shifts potassium out of the skeletal muscle cells.

    hyperkalaemia induces arterial dilation, which increases skeletal muscle blood flow and acts as an adaptive mechanism during exercise.

    In patients with pre-existing potassium depletion, post-exercise hypokalemia may be severe and rhabdomyolysis may occur.

  • Hypokalemia (serum K < 3.5 mmol/L)

    routine serum electrolyte measurement. deficit in total body K stores

    abnormal movement of K into cells.

    Hypokalemia is a common clinical problem!

    The cause of which can usually be determined from the history (as with diuretic use, vomiting, or diarrhoea). In some cases, however, the diagnosis is not readily


  • Serum K measurement


    Detailed history to search for