Serum potassium is a very finely regulated value. Indeed, the transmembrane resting potential of nerve and muscle cells is directly related to the concentration differential between intracellular potassium and extracellular potassium. If the kalemia rises, the resting potential of the cells decreases, increasing the excitability of the cells.
The potassium concentration depends on two variables: the total amount of potassium in the body and the distribution of potassium in the intracellular and extracellular areas.
The amount of potassium (K + ) in the body depends on the balance of input / output that remains at equilibrium in the normal subject. The kidney is the sole organ of control of the body’s potassium homeostasis.
DISTRIBUTION OF POTASSIUM IN THE ORGANISM:
K + is 95% located in the cell compartment, mainly in muscle cells (78%), in liver cells (6%) and in red blood cells (6%). Only 2% is located in the extracellular compartment.
In cells, the K + concentration is maintained very high, of the order of 120 to 150 mmol / L of cellular water. This is done by the activity of membrane Na / K ATPase. The intracellular K + is accompanied by protein anions, phosphates and organic anions.
In the extracellular medium, serum potassium is kept low between 3.5 and 4.5 mmol / L.
The value regulated by the organism is the ratio of potassium concentrations on both sides of the cell membrane (kalemia / kalicysis ratio). Indeed, it is from this ratio that the value of the membrane potential, a key element of excitability and muscle contraction (whether striated, smooth or cardiac muscle) depends.
the extracellular potassium / potassium intracellular ratio and not the serum potassium. However, although the regulated value is the intracellular extracellular potassium / potassium ratio, in fact, regulation is limited to serum potassium because significant fluctuations in the amount of intracellular K + are rarely observed.
POTASSIUM INPUTS AND OUTPUTS:
The only entry of potassium is diet, potassium being a major constituent of plant and animal cells. The daily intakes are 50 to 150 mmol / d. The digestive absorption of ingested potassium is complete.
There are extrarenal and renal exits. Extrarenal outflows that are not regulated are mainly through digestive secretions. However, they correspond to only 5 to 10% of potassium ingested due to the low water content of normal stools. The digestive output of potassium can become very important in pathology (diarrhea, vomiting, etc.). The other extrarenal release of potassium is sweat. It is very poor in potassium.
Potassium releases correspond to 90% of ingested potassium. This output is finely regulated.
In the normal state, the potassium input / output balance is stable, the urinary excretion is equal to the digestive absorption.
INTERNAL BALANCE OF POTASSIUM:
The internal balance concerns the movements of the potassium ion on either side of the cell membrane under the action of physiological or pathological processes.
Sometimes, in one meal, the total potassium content of the extracellular area is ingested (50 mmol). Within 15 to 30 minutes after a meal, more than 70% of the ingested potassium is transferred to the cells. The elements that participate in this internal balance are hormones, neurotransmitters, acid-base balance and osmolality.
It has a permissive role on the entry of K + in the cells by stimulating the entry of Na + into the cell by the membrane Na + / H + exchanger. Intracellular Na + elevation secondarily stimulates the Na / K ATPase, resulting in a clear K +uptake into the cell.
It improves tolerance to a potassium load by promoting cell sequestration of K + and promoting K + secretion by the colon.
They have a permissive role on the entry of K + into the cell by stimulating Na / K ATPase.
It plays a major role in the movements of K + on both sides of the cell membrane. In the course of acidosis and alkalosis, the transmembrane movements of K + depend on the intracellular diffusibility of the ion which accompanies the H + ion.
Acute metabolic acids:
In acute mineral metabolic acidosis, ie characterized by the addition of H + and Cl – ions in the extracellular space (diarrhea), the proton diffuses into the cell while the Cl – can not penetrate. Respect of the intracellular electroneutrality requires the output of a potassium ion or a sodium ion. The resulting increase in serum potassium varies widely from one subject to another from 0.2 to 1.7 mmol per 0.1 unit of pH decrease.
In the course of acute metabolic acidosis by the addition of organic acid (lactic acidosis), the proton penetrates the cell with the accompanying cation, which does not result in a K + cell outcome. Lactic acidosis is therefore not accompanied by hyperkalemia. If this is present, the etiology must be investigated: renal insufficiency, hypercatabolism, etc.
Chronic metabolic acidosis:
They cause hypokalaemia by increasing renal excretion of K + (see below).
CO 2 , which diffuses very easily through the cell membranes, respiratory acidosis is not accompanied by hyperkalaemia.
Acute respiratory alkalosis:
There is no change in serum potassium.
Chronic respiratory syndrome:
Hypokalemia is constant but moderate. It is secondary to a urinary leakage of potassium (cf infra).
The addition of NaHCO 3 in the extracellular sector induces hypokalaemia because the HCO 3 ion can not diffuse into the cell. The output of a proton from the cell will therefore lead to the entry of a K + into the cell. In addition, metabolic alkalosis induces a significant urinary loss of K + (see below).
In total, insulin and catecholamines are the two main hormones regulating, in physiology, the internal balance of K + .
Renal potassium behavior:
Urinary excretion of K + is equal to the difference between filtered K + and K + reabsorb plus K + secreted:
Urine excretion K + = K + filtered – K + reabsorbed + K + secreted The filtered K + is equal to the product of the glomerular filtration rate
(GFR) by serum potassium:
K + filtered = DFG ‘ kalemia = 180 L / d ‘ 4 mmol / L = 720 mmol / d
The Western diet provides between 50 and 100 mmol / d of K + , which corresponds to the same urinary excretion, ie only 5 to 15% of the filtered amount. There is thus essentially a renal reabsorption of K + .
In case of large intakes, the amount of excreted K + may exceed the amount filtered, indicating a net tubular secretion.The amount excreted can be up to 200% of the filtered K + .
PROXIMAL CONVERSION TUBE:
Regardless of the K + intake , the proximal bypass tube (TCP) will reabsorb between 55 and 60% of the filtered K + .
The reabsorption is carried out by paracellular passive diffusion along the chemical gradient. The chemical gradient of K + reabsorption is created by basolateral Na / K ATPase. By promoting the reabsorption of Na + , it leads to a decrease in the osmolality of the tubular fluid, which promotes a passive reabsorption of water. Once the water is reabsorbed, the concentration of K + in the tubular fluid rises, which causes K + reabsorption along its chemical gradient.
WIDE HIKING DIVISION AND DISTAL TUBE:
Regardless of the K + intake , the broad ascending limb of the loop of Henlé and the distal tube will reabsorb between 30 and 40% of the filtered K + .
Reabsorption is achieved by two mechanisms:
– paracellular passive diffusion related to the positive light transtubular potential difference;
– cotransport Na + / K + / 2Cl – , made possible by the activity of the basolateral Na / K ATPase which leads to the reabsorption of Na + ; the decrease in the osmolality of the tubular fluid leads to an increase in the K + concentration of this fluid, thus reabsorbing K + along the chemical gradient by the transcellular route.
CORTICAL COLLECTOR TUBE:
The cortical collector tube (TCC) contains three cell types:
– the main cells, responsible for the secretion of K + , the most numerous;
– alpha intercalating cells which reabsorb K + at the same time as they secrete protons (H + / K + luminal ATPases);
– intermediate cells which could secrete K + at the same time as HCO 3- ions (basolateral H + ATPases).
In TBI, if the K + intake is “standard”, a small secretion occurs; if the intake of potassium is low, the secretion is abolished and reabsorption up to 99% of the filtered K + will occur; if the potassium intake is massive, a very important secretion will occur.
Urinary excretion of potassium depends on two factors:
The concentration of K + in the tubular fluid;
– the flow of tubular fluid.
The concentration of K + in the tubular fluid is dependent on the secretion of K + in the TCC, a secretion linked to three elements:
– an electrogenic reabsorption of Na + which generates a difference of transtubular potential to negative light;
A chemical concentration gradient of K + between cell and tube lumen;
– K + movements through specific channels of the apical membrane of the main cells.
Passive secretion by the main cells:
The basolateral Na / K ATPase maintains the high intracellular K + concentration while that of Na + is low. Na +diffuses into the main cell more rapidly than Cl – due to specific Na + channels in the luminal membrane (called “electrogenic” reabsorption). This channel called the “epithelial sodium channel” is sensitive to amiloride. These elements explain that the difference of transtubular potential is clearly negative light in this tubular segment, which allows the secretion of K + .
The K + will passively diffuse from the cell to the tubular lumen through the potassium channels. These potassium channels are open in case of important potassium intakes and under the action of aldosterone and vasopressin.
Active reabsorption by alpha spacer cells:
The H + / K + ATPase luminal secretes protons, which ensures active reabsorption of K + . Once in the cell, K + will passively diffuse to the interstitial fluid through basolateral potassium channels. However, in physiology, net reabsorption of potassium by alpha intercalated cells is low.
Factors influencing urinary excretion of potassium:
Dietary intake of potassium results in an increase or decrease in urinary excretion of potassium by the kidney directly related to the amount of potassium ingested.
When the intake of potassium is high, we see:
An increase in the number and activity of the Na / K ATPase located on the basolateral membrane of the main cells, which increases the chemical concentration gradient between the cell and the tubular lumen;
– a secretion of aldosterone which will stimulate the tubular secretion of potassium (cf infra).
In the case of low K + inputs, inverse events occur.
QUANTITY OF NA + DELIVERED TO THE DISTAL AND MINERALOCORTICOIDS TUBULA:
Changes in Na + intake did not alter the urinary excretion of K + . This lack of effect can be explained by the inverse variations of aldosterone.
The aldosterone increases the secretion of potassium through the cortical collector tube by directly stimulating the Na / K ATPase and increasing the number of sodium channels in the apical membrane. The aldosterone actually prevents the variations of kaliuresis related to the sodium intake. In the case of significant sodium intakes, the increase in the tubular flux leads to tubular secretion of potassium. However, since aldosterone secretion is inhibited, potassium leakage is limited. In the case of weak sodium intakes, the opposite situation is observed.
They do not stimulate renal excretion of K + . The most likely reason for this is that the main cells possess an enzyme, 11- α- hydroxy steroid dehydrogenase (11- α -HSD), which metabolizes glucocorticoids to metabolites devoid of affinities for the mineralocorticoid receptor.
Glucocorticoids cause potassium to escape from the cell with sodium and water. This outcome favors the urinary excretion of K + observed under corticosteroids at the usual dosages.
BICARBONATES IN THE URINES:
Bicarbonatura promotes urinary secretion of K + . The secretion of K + appears to be related to the presence of an alkaline tubular fluid, particularly in the presence of HCO 3- .
This is confirmed by
the fact that in the clinical situations associated with the presence of HCO 3 in the tubular fluid of the cortical collecting tube (vomiting, tubular acidosis, etc.), an abnormally high urinary excretion of K + is present.
ANTIDEURETIC HORMONE / VASOPRESSINE:
The antidiuretic hormone (ADH) stimulates the net secretion of K + by the main cells, by increasing the apical permeability of the sodium channels. Yet ADH does not increase urinary excretion of potassium.
In hydropenic conditions, the tubular flux is greatly diminished, which is a very limiting factor of potassium excretion. In this situation, the stimulated ADH will maintain the potassium balance by stimulating the secretion of K + .
In water-stressed conditions, the tubular flow is important (which increases the excretion) but the absence of ADH limits the secretion of K + .
As a rule, alkalosis promotes excretion of K + while acidosis reduces it.
Effects of alkalosis in general:
Alkalosis increases the secretion of K + in TCC by two direct effects on the main cells:
– alkalosis stimulates Na / K ATPase; the cells of the TCC behave like all the cells of the organism since, under the effect of the alkalosis, the entry of K + in the cell is stimulated;
– alkalosis increases the permeability of the apical membrane to K + by increasing the opening of the potassium channels.
Chronic metabolic alkalosis causes severe potassium depletion due to elevated urinary excretion. In contrast, the initial kaliuretic effect of respiratory alkalosis is transient and moderate.
Effects of acute respiratory or metabolic acidosis:
These are exactly the inverse effects of alkalosis, with inhibition of Na / K ATPase and decrease in the number of potassium channels on the luminal membrane
Chronic metabolic acidosis:
It leads rather to a hypokalaemia secondary to a renal leakage of K + by:
– an increase in the tubular flow, which is explained by the decrease in the filtered amount of HCO 3 responsible for a reduction in sodium reabsorption by Na + / H + exchange in the proximal tube from which the increase in quantity delivered of sodium and water to TCC;
– hyperaldosteronism secondary to the loss of urinary sodium causing a contraction of the extracellular volume.
EXPLORATION OF DYSKALIEMIA:
Urinary excretion of K + depends on two factors:
The concentration of K + in the tubular fluid of the TCC;
– the flow of tubular fluid in the TCC.
Kaliuresis is the product of the concentration of K + in the TCC fluid ([K] TCC ) by the flow of fluid in the TCC (Q TCC ):
K U = [K] TCC ‘ Q TCC
It is possible to calculate the value of the two components of the equation. The benefits of this approach, which we owe to the Canadian physiologist Halperin, are manifold. Indeed, the “standard” of exploration of dyskalaemia rests on the urinary excretion of K + over 24 hours. However, the latter is often faulted.
For example, in the exploration of hypokalaemia, the loss of K + may have occurred in the recent past and may not be reflected in the current composition of the urine. Similarly, it is not possible to know which component of kalauresis (increase in K + concentration or flow in CBT) is responsible for a renal leakage of K + .
The two components of the equation can be calculated from the moment the urinary osmolality is greater than the blood osmolality, which means that the ADH acts. Indeed, in this situation where DHA is present, the major component that determines the water flow in the TCC is the excretion flux of the osmoles (electrolytes and urea). Assuming that these osmoles are not reabsorbed in the medullary part of the collecting tube, the water flux can be estimated by dividing the osmolar flow by the osmolality at the end of the TCC (which is equal to the osmolality of the plasma when l ADH acts).
If the dyskalemic patient to be investigated has diluted urine (osmolality [OsmS] less than osmolality blood [OsmS]), re-examinations after water restriction, which will allow to concentrate the urine.
Reminders of osmolality formulas:
OsmS: 2 ‘ Natremia + 10
OsmU: 2 ‘ (Na + + K + ) + Urea
Na + , K + and urea are the concentrations in mmol / L.
In this way,
– water flow in the TCC (Q TCC ):
Q TCC = Osmu / OsmS ‘ diuresis (L / d)
Example: OsmU: 430 mOsm / L
OsmS: 280 mOsm / L diuresis = 1.5 L / d
Q TCC = 430/280 ‘ 1.5 = 2.30 L / d
– the osmolar flow in the TCC:
Q osm TCC = Q TCC ‘ OsmS (mOsm / j)
In our example, Q osm TCC = 2.30 ‘ 280 = 645 mOsm / d
There are no true normal values of water flux and osmolar flow in TBI since these values depend on water intake and feeding, which vary from one subject to another.
In a 60 kg patient with a standard feed, the water flux in the CBT is 3 to 4 L / d and the osmolar flux is 600 to 1000 mOsm / d.
The transtubular gradient of K (GTTK):
This gradient represents the “strength” of K + secretion in TCC main cells. It is directly reflective of the secretion linked to the three elements (see above):
– electrogenic sodium reabsorption;
– chemical concentration gradient of K + between cell and tube lumen;
– K + movements through specific channels of the main cells.
GTTK is the ratio of urinary concentration of K + to serum potassium, which is corrected by the ratio of urinary osmolality to blood osmolality. This correction makes it possible to take into account the reabsorption of water in the medullary part of the collecting tube.
GTTK = [K U ] x Osm S / Osm U ‘ [K s ]
GTTK is more reliable than the excretion fraction of K + because the latter depends on the reabsorption of water throughout the nephron whereas the GTTK depends only on the reabsorption of water at the medullar collector tube .This makes it possible to analyze transport of K + (secretion or reabsorption) in TCC.
The GTTK is reliable despite the fact that it does not account for the reabsorption of K + and osmoles in the medullary collector tube. In fact, in the vast majority of clinical situations, reabsorption of K + and osmoles in the medullary collector tube is too weak to modify the GTTK.
As with Q TCC and Q osmTTC , there is no normal GTTK value. However, this is in healthy subjects with a normal diet between six and 12. In case of a zero intake in K, it can be lowered to one. In case of potassium loading, it can rise up to 15.
In the hypokalemic patient, it must be less than two. If this is not the case, it means that the kidney is totally or partially responsible for hypokalaemia.
In the hyperkalaemic patient, the GTTK must be greater than ten.
If this is not the case, it means that the kidney is totally or partially responsible for hyperkalaemia.
Renal dyskalaemia (this is by far the most frequent cause of serum potassium anomalies) can have two origins:
– an inadequate GTTK;
– an abnormal flow of fluid in the TCC.
In pathology, a GTTK that is too high with regard to hypokalaemia can come from two elements:
– too rapid reabsorption of Na + with respect to Cl – in TCC, which leads to raising the difference of transepithelial potential to negative light and thus to promoting the secretion of K + ; the classic example is primitive hyperaldosteronism where, under the influence of aldosterone, Na + is eagerly reabsorbed;
– too slow reabsorption of Cl – compared to Na + in TCC, which leads to raising the difference of transepithelial potential to negative light and thus to promoting the secretion of K + ; this phenomenon occurs, for example, in clinical situations where bicarbonate ions are present in TCC (vomiting), bicarbonate ions inhibit the reabsorption of Cl – ions (by an unknown mechanism).
In pathology, a GTTK that is too low with respect to hyperkalaemia can come from two elements:
– too slow a reabsorption of Na + with respect to Cl – in TCC, which leads to decrease the difference in transepithelial potential to negative light and thus to inhibit the secretion of K + ; the classic example is primitive hypoaldosteronism, in which, in the absence of aldosterone, Na + is not reabsorbed: the same is true in the case of closure of the sodium epithelial channels under the effect of amiloride;
– too rapid reabsorption of Cl – compared to Na + in TCC, which leads to decrease the difference in transepithelial potential to negative light and thus to inhibit the secretion of K + ; this phenomenon occurs, for example, in hyporenine-hypoaldosterone syndromes characterized by significant chlorinated reabsorption.
Abnormal fluid flow in TCC:
A hypokalemic patient due to an unavowed intake of diuretics will have a high fluid flow in the TCC while the GTTK will be normal.
Conversely a patient following scrupulously a salt-free diet will have a low fluid flow in the TCC with a normal GTTK.
In total, the basic exploration of dyskalaemia requires:
– a blood ionogram with an alkaline reserve;
– blood urea;
– a urinary ionogram with urinary urea (by quantifying the 24-hour diuresis).
These elements make it possible to easily calculate Q TCC , Q osm TTC and GTTK.
Possibly and in second intention, one will ask:
– blood gases;
– a dosage of magnesemia;
– a dosage of renin and aldosterone;
– tests with Synacthene or 9 alpha -fludrocortisone.
A patient is hypokalemic if the serum potassium concentration is less than 3.5 mmol / L. In the vast majority of cases, hypokalemia is discovered on a systematic review, but sometimes there is a clinical symptomatology dominated by muscle signs.
The clinic is limited to a systolic murmur, an increase in blood pressure differential by diastolic decrease and orthostatic hypotension. Cardiac involvement should be systematically investigated on the electrocardiogram. This one can show:
– a subsidence of the ST segment;
A decrease in the amplitude of T;
– the appearance of the U wave.
If the differential between kalaemia and kalicystia is significant, the electrocardiogram will reveal more severe rhythm disorders: atrial fibrillation, ventricular extrasystoles, ventricular tachycardia and fibrillation, and torsades de pointe.
It is recalled that the toxicity of digitalis is increased in case of hypokalaemia.
Impairment of smooth muscle and striated muscle:
Hypokalemia can cause a paralytic ileus of the gastrointestinal tract, hypotonia with decreased muscle strength, tetany, and pseudoparalysis. Finally, hypokalaemia favors rhabdomyolysis.
Acute hypokalemia has no renal impairment. On the other hand, in some chronic hypokalemic patients, there is a decrease in urine concentration and decreased renal blood flow and glomerular filtration rate. The renal histology finds a vacuolation of the proximal tubular cells and of the collecting tube which can regress after correction of the potassium deficiency. Can be associated with: edema and interstitial fibrosis and focal cellular infiltrates.
Chronic hypokalemic interstitial nephritis can be explained by the urinary tract infection. Indeed, the tubular cells in case of hypokalemia defend themselves less well against the bacteria. In addition, hypokalemia stimulates the formation of NH 4+ , which activates the complement which can cause interstitial lesions.
Etiologies of hypokalemias:
They are of four types:
– lack of contribution;
– transfer hypokalaemia;
– digestive losses of K + ;
– renal losses of K + .
Deficiency of supply:
It can be observed in the case of total fasting or in the resuscitation patient in the absence of parenteral intake in K. The serum potassium concentration decreases by 1 mmol / L approximately, with a suitable renal response (GTTK <2).
Potassium depletions of digestive origin:
· Acute and chronic diarrhea, villous tumors, digestive fistulas
During acute diarrhea, hypokalaemia with hyperchloremic metabolic acidosis is observed because the stools are rich in K + and HCO 3- . In this case, the Q TCC is low, as is the
GTTK, indicative of the appropriate renal response.
During chronic diarrhea and the abuse of laxatives, the situation is much less clear. Hypokalemia is constant but may be accompanied by either metabolic acidosis (the most typical situation) or metabolic alkalosis. An alkalosis is observed when the abuse of laxatives associates with an unavowed intake of diuretics or induced vomiting.
If hypokalemia is accompanied by chronic metabolic acidosis, GTTK is unsuitable for serum potassium. The elevation of Q TCC secondary to the renal leakage of Na + also contributes to renal leakage of K + . If hypokalaemia is accompanied by metabolic alkalosis, GTTK is also unsuitable. Q TCC is also high with osmoles consisting essentially of K + .
· Vomiting and gastric aspiration
There is hypokalaemia with metabolic alkalosis. The renal response is stereotyped with an inadequate GTTK due to bicarbonatura and a variable QT. This is either low due to extracellular dehydration (adapted response) or high due to the leakage of Na + with HCO 3- to the active phase of vomiting.
Potassium depletions of kidney origin:
· Rapid reabsorption of Na +
They are characterized by an inadequate GTTK while the Q TCC is normal. However, the latter may increase if the Na + intake increases, which increases or causes hypokalemia.
On the clinical side, the elucidative reabsorption of Na + explains the tendency to inflation in the extracellular sector with sometimes hypertension (hypertension). Renin is always low with a variable aldosterone depending on the etiology.
The etiologies are listed below.
Primary hyperaldosteronism or Conn syndrome.
On the endocrine level, it is characterized by a low and non-stimulable renin and a high aldosterone.
This syndrome may be related to:
– Adrenal adenoma;
– bilateral adrenal hyperplasia;
– adrenal cancer.
Another condition characterized by hypertension and hypokalaemia gives the same hormonal profile. This is the dexamethasone-sensitive HTA (DXM) also called hyperaldosteronism suppressible by DXM. This rare familial disease, with autosomal dominant transmission, is due to the presence of a chimeric gene whose activity is that of aldosterone synthetase and tissue specificity that of 11 ? -hydroxylase. There is therefore an increased production of ACTH-dependent mineralocorticoid compounds which can be reduced by small doses of DXM and an antialdosterone.
Syndromes related to primitive hyperaldosteronism.
On the endocrine level, they are characterized by low renin and low aldosterone.
Enter this category:
– Cushing’s syndrome;
– the deficiency acquired by hydroxysteroid dehydrogenase from glycyrrhizin intoxication;
– the hereditary deficiency in 11-hydroxysteroid dehydrogenase also called apparent mineralocorticoid excess syndrome.
These three conditions are characterized by an acquired or hereditary deficiency of the 11-hydroxysteroid dehydrogenase which no longer metabolizes the glucocorticoids, which allows them to have a mineralocorticoid effect, hence HTA and hypokalaemia.
Also belonging to syndromes related to primary hyperaldosteronism:
– congenital adrenal hyperplasia due to 11-hydroxylase or 17 alpha -hydroxylase deficiency;
– Liddle syndrome.
Liddle syndrome is a rare, autosomal dominant condition that causes severe hypertension. It is related to a genetic mutation of the sodium epithelial canal sensitive to amiloride, which will lead to a volemic expansion. The treatment is based on the salt-free diet and the K + saving diuretics.
Note that secondary hyperaldosteronism with hypertension (renin tumors, malignant hypertension, renal artery stenosis) or without hypertension (nephrotic syndrome, hepatic cirrhosis, heart failure) is not usually accompanied by hypokalaemia. Indeed, in these situations, the decrease in QT CT largely offsets the kaliuretic effect of hyperaldosteronism (which elevates the GTTK).
· Slow reabsorption of Cl –
Deletions are characterized by an inadequate GTTK while Q TCC is normal. On the clinical side, the too slow reabsorption of Cl – explains the tendency to dehydration of the extracellular sector with sometimes hypotension.Renin is always high.
The etiologies are listed below.
This is an autosomal recessive disorder related to an anomaly of the Na + / K + / 2Cl cotransporter – of the ascending branch of the cove of Henlé. Diagnosis is often made during early childhood in front of a picture in every point comparable to that of a patient under diuretic of the loop: leaked soda urinary, hypokalemic alkalosis, normomagnesemia and hypercalciuria.
It is an autosomal recessive disorder related to an abnormality of the Na + / Cl – cotransporter in the distal tube, which is usually diagnosed in young adults. This defect is at the origin of a clinical picture at all points identical to that of a patient under thiazide diuretic with urinary soda leak, hypokalemic alkalosis, hypomagnesemia and hypocalciuria.
It may be accompanied by hypokalemia, the pathogenesis of which is unknown. Correction of magnesium deficiency allows correction of hypokalaemia.
Clinical situations characterized by bicarbonaturia:
– proximal and distal tubular acidosis;
– treatment with acetazolamide
Chronic metabolic acidosis.
Treatment with amphotericin B (Fungizone)
The hypokalaemia due to amphotericin B by the parenteral route could be explained by the insertion of the molecule in the luminal membrane of the renal tubular cells. This leads to sodium leakage, hypomagnesemia and tubular acidosis.
· Increase QTCT
The etiologies are thiazide diuretics and the loop, high sodium chloride intakes (in these two situations, the elevation of Q osmTCC is related to Na and Cl ions), osmotic diuresis with exogenous urea, glycosuria, mannitol (in these situations, elevation of Q osmTCC is related to molecules that are not reabsorbable or whose reabsorption is limited).
· Metabolic and respiratory alkalosis
In the case of chronic metabolic or respiratory alkalosis, hypokalaemia can be explained by two mechanisms:
Transfer of K + into the cells;
– GTTK elevated by too rapid Na + reabsorption or by too slow reabsorption of Cl – depending on the etiology of alkalosis.
· Excess insulin and renutrition
When administering exogenous insulin to a diabetic patient, transfer hypokalemia may occur for a few hours.
In the case of renutrition of a malnourished subject, multifactorial hypokalemia may occur due to the administration of glucose and the reconstitution of muscle mass.
· Hypokalemic periodic palsy or Westphal disease
This is an autosomal dominant condition associating access of lower limb and trunk paralysis to transfer hypokalaemia with low GTTK. The crisis began during the second decade. Seizures are often triggered by a high carbohydrate meal, rest after exercise, infection or alcohol consumption. Prevention relies on the elimination of the triggering circumstances of seizures and the K + -depositing diuretics.
· Chloroquine poisoning
During chloroquine poisoning, hypokalaemia is frequently observed, probably in relation to an intracellular transfer of K + in spite of a rather acidic blood pH.
The treatment of hypokalaemia is obviously the cause of its cause.
Symptomatic treatment is based on the intake of K + which can be achieved by feeding. Fresh and dry fruits and vegetables are rich in K + . Milk, meat and potatoes contain less K + .
Intravenous potassium recharge can use all K + salts: K + chloride, K + citrate, K + gluconate and monopotassium phosphate.
In case of renal leakage in K + , antikaliuretic diuretics are very useful. Spironolactone (Aldactone t ) is used in the case of hyperaldosteronism or amiloride (Modamide t ) in the absence of hyperaldosteronism.
Antikaliuretic diuretics are formally contraindicated in patients with minimal renal insufficiency.
Any patient with serum potassium greater than 5 mmol / L is hyperkalaemic. Attention should be paid to dosage errors related to hemolysis in case of difficult venipuncture or prolonged tourniquet.
In the vast majority of cases, hyperkalaemia is discovered on a systematic assessment but sometimes there is a clinical symptomatology dominated by the muscular signs.
It is highlighted on the electrocardiogram by:
An increase in the amplitude of the T wave;
A decrease in the amplitude of the P-wave, then disappearance;
– lengthening of the PR space (atrioventricular block);
– enlargement of QRS (intraventricular block);
– disorders of the ventricular rhythm: tachycardia or flutter or ventricular fibrillation.
Some authors define stages:
– stage 1 (serum potassium concentration around 6 mmol / L): amplitude increase of the T wave;
– Stage 2 (6 to 7 mmol / L serum potassium): disappearance of P and widening of QRS;
– stage 3: intraventricular block and slow heart rate;
– stage 4: complete atrioventricular block, circulatory arrest.
They often occur at the same time as the cardiological signs: paresthesia of the extremities, flaccid paralysis, symmetrical with muscular hypotonia.
Etiologies of hyperkalaemia:
There are two major types of hyperkalaemia etiologies:
– hyperkalemias due to the absence of potassium excretion, the most frequent;
– hyperkalaemia by cell transfer.
Hyperkalaemia by default of renal excretion of K +:
The K + excretion deficiency may be related to either an inadequate GTTK (K + secretion capacity in the TCC too low) or a decrease in water flow in the TCC, as the two disorders may associate.
· Hyperkalaemia by inappropriate GTTK
They are characterized by a GTTK of less than ten while the Q TCC is normal. However, the latter may decrease if sodium chloride is low, which may increase hyperkalaemia.
Slow reabsorption of Na +
In this situation, dehydration of the extracellular area is often present in relation to a renal leakage of Na + , renin is elevated. The aldosterone is variable according to the etiology.
The etiologies are:
– adrenal insufficiency or Addison’s disease (low aldosterone);
– decreased bioavailability of aldosterone induced by many drugs: ACE inhibitors, Heparin t (which decreases the number and affinity of angiotensin II receptors in the glomerulus the adrenal), Spironolactone t ;
– closure of epithelial sodium channels; many drugs are involved: amiloride, triamterene, trimethoprim, pentamidine;
– a rare condition: type 1 pseudohypoaldosteronism; this autosomal dominant disease is due to a deficit in the cellular action of aldosterone. The diagnosis is made shortly after birth in front of a table associating urinary leak soda, hypotension, hyperkalaemia and elevation of aldosterone very important;
– congenital adrenal hyperplasia by enzymatic deficiency in 25-hydroxylase.
Reabsorption of Cl –
In this situation there is a tendency to hyperhydration of the extracellular sector by renal retention chlorosodium, renin is low.
The etiologies are:
– certain drugs such as nonsteroidal anti-inflammatory drugs or ciclosporin;
– severe renal insufficiency: if the potassium intake is normal, the renal insufficiency patient develops hyperkalaemia only for glomerular filtration rate values below 5 mL / min;
– hyporenine-hypoaldosterone syndromes observed during diabetic nephropathy, obstructive uropathies, certain interstitial nephropathies or acute glomerulopathies (lupus erythematosus, for example); hyporenine hypoaldosterone syndrome is readily observed in the elderly with a decreased adrenal response to hyperkalaemia;
– Gordon syndrome or pseudohypoaldosteronism type 2; it is a rare autosomal dominant disorder characterized by hypertension with hyperkalaemic acidosis; thiazide diuretics are used to correct hypertension and hyperkalemia.
· Decrease Q TCC
During these conditions, the Q TCC is low whereas the GTTK is adapted (greater than 15).
The etiologies are as follows:
– dehydration of the extracellular sector and reduced sodium intake; in this case Q osmTCC is low due to urine poverty in Na + and Cl – ;
– limited protein diets and anabolic situations where the urea load in CBTs will be low, resulting in a low Q osmTCCdue to low urinary urea.
Hyperkalemias by cell transfer:
The etiologies are:
– mineral acidosis;
– unbalanced diabetes;
– cell destruction (rhabdomyolysis, muscle crushing, extensive burns, hemolysis, tumor lysis, digestive bleeding) which can not be accompanied by hyperkalaemia unless there is a K + excretion disorder;
– digitalis (inhibition of Na / K ATPase), beta-blockers;
– the familial periodic paralysis of Gamstorp which resembles Westphal disease but whose paralytic access is accompanied by hyperkalaemia.
The treatment of hyperkalaemia is obviously the treatment of its cause. Different symptomatic treatments can treat hyperkalaemia itself.
Means of treating hyperkalaemia:
Diet low in K +
Calcium salts. They reduce the effects of hyperkalemia without lowering serum potassium. Moreover, their effect is transient, only during the time of the increase in serum calcium that they cause. 10% calcium gluconate can be used 10 to 30 mL intravenously. Calcium salts are contraindicated if the patient is under digitalis.
Cation exchange resins. Sodium polystyrene sulphonate (Kayexalate) is administered 30 to 120 g / d (three to four times) orally or rectally (enemas to be kept 4-8 hours). It is a powder to be diluted in water, knowing that 1 g of Kayexalate exchanges 1 to 2 mmol of K + for 1 to 2 mmol of Na + . Because of sodium intake, hypertension and heart failure are relative contraindications.
Calcium sorbisterite has the same properties as Kayexalate but exchanges K + for Ca ++ .
Alkalizing. We can use :
– water from Vichy;
The 1.4% (molar) HCO 3 Na which brings 165 mmol / L of Na + and HCO 3 ;
The HCO 3 Na at 4.2% (three times molar);
Na mole lactate (1,000 mmol / L Na + and HCO 3 ).
All these solutes contain significant quantities of Na + and therefore can not be used in cardiac insufficiency or in cases of oligoanuria.
Joint supply of insulin and glucose. The effect is temporary because after glycogen synthesis, it is degraded to glucose with a resurgence of serum potassium. The dosage is 500 mL of G 30% with 15 units of insulin to pass in 1 hour.
Extrarenal treatment by hemodialysis or peritoneal dialysis. It is the most effective and fastest way to reduce serum potassium.
Betamimetics. They cause a moderate decrease in serum potassium.
Of inconsistent efficiency, they are very little used.
Diuretics of the loop or thiazides. They can be used in patients with vascular overload with mean hyperkalaemia.
In the case of moderate hyperkalemia, the treatment is based on the decrease in K + intake , Kayexalate t and Vichy water.
If hyperkalaemia is moderate, it may be alkalized with HCO 3 Na or insulin / glucose.
In case of severe hyperkalaemia and in the absence of vascular overload, use Na + lactate and insulin / glucose intake preceded by calcium gluconate. Extrarenal scrubbing is often necessary.
In case of severe hyperkalaemia in the presence of signs of vascular overload, the use of extrarenal purification techniques is mandatory.