STUDY - Technical - New Dacian's Medicine
Fluid
and Electrolyte Imbalances (5)
Translation Draft
A more consistent post will follow because I want to finish as soon as possible with all this "chemistry" of electrolyte balances, especially important for the "approaches" to come.
As we announce, we will proceed to the study of potassium, starting with its balance in the body. Potassium (K) is the most important intracellular cation. The normal concentration of K+ in plasma is between 3.5 - 5 mmol/ l, while in cells it is about 150 mmol/ l. Therefore, the amount of K+ in the FEC (between 30 and 70 mmoli) represents less than 2% of the total K+ content of the body (between 2500 - 4500 mmol). The ratio of K+ concentration in FIC and FEC (normally 38:1) is the main result of resting membrane potential and is essential for normal neuromuscular functioning.
The Na+, K+ - ATP-ase basal pump actively transports K+ inside the cell and Na+ outside it in 2:3, and the passive outward diffusion of K+ is quantitatively the most important factor that generates the resting membrane potential. The activity of the Na+, K+ -ATP-ase electrogenic pump may be stimulated as a result of increased intracellular Na+ levels and may be inhibited in the case of digital toxicity or chronic conditions such as heart failure or renal failure.
K+ distribution is also affected by many other factors, including hormones, acid-base balance, osmolarity and cellular turn-over. Insulin increases the activity of the pump Na+, K+ - ATP-acivil indirectly and independently of its effects on glucose transport, leading to the entry of K+ into muscle and liver cells. In contrast, insulin deficiency causes K+ from the FIC compartment to the FEC.
Catecolamines have variable effects on the distribution of K+ - beta2 agonists - adrenergic stimulating, while alpha adrenergic agonists inhibit the collection of K+ by cells. The Na+, K+ pump - ATP-ase, as well as insulin secretion, are stimulated by beta2- adrenergic agonists. In contrast, alpha adrenergic agonists have the opposite effect. The main action of aldosterone is to increase the excretion of K+. The role of extracellular pH in the K+ balance is linked to underlying acid-base imbalances. In metabolic acidosis, 60% of the amount of H+ is buffered intracellularly.
To maintain electroneutrality, H+ ions are either accompanied by an anion or are exchanged with intracellular K+ (leading to hyperpotasemia). Organic acidosis is not commonly associated with a pH-related K+ exchange, as anions such as lactate or beta-hydroxybutyrate can be quickly picked up by the cell. K+ entry into the cell can be quickly observed in metabolic alkalose. However, this exchange is less important due to the decrease in intracellular buffering.
Primary respiratory disorders of acid-base balance cause a minimum transcellular transport of K+. In situations of hyperosmolarity, K+ diffuses into the extracellular space together with the water that thus constitutes the "pulling solvent". The concentration gradient, which favours the passage of K+ into the extracellular space is also increased as a result of water loss from fic. Tissue destruction or catabolism causes the release of intracellular K+, while in the formation of new cells K+ is used from the FEC level.
Finally, moderate or increased exercise may be associated with the release of K+ from the muscles, leading to glycogenolosis and local vasodilation. This is normally transient, but may affect the plasma concentration of K+ if the patient repeatedly squeezes and loosens the fist before the venous puncture.
Ingestion of K+ in an average Western diet is 40 to 120 mmoli/ day or about 1 mmol/ kg/ day, 90% of which is absorbed through the gastrointestinal tract.
Maintaining a balance requires a correlation between ingestion and secretion of K+. Initially, extrarenal adaptive mechanisms and then urinary excretion prevent the doubling of the plasma concentration of K+, which could occur if the entire amount of K+ in the diet remained in the FEC space. Immediately after the meal, the vast majority of the absorbed K+ enters the cells as a result of the initial increase in the plasma concentration of K+, the process being favored by the release of insulin and the basal levels of catecholamines.
An excess of K+ is excreted through urine. The regulation of intestinal absorption of K+ is not fully understood. The amount of Lost K+ caught stool can increase from 10 to 50 or 60% (from daily intake) in chronic renal failure. In addition, colonic secretion of K+ is stimulated in patients with large amounts of diarrhoea and can lead to severe K+ discharge.
Excretion of K+ occurs mainly through renal excretion which is the main route of removing excess K+ from diet or other sources. The amount of K+ filtered is 10-20 times the K+ content of the FEC. 90% of the filtered K+ is reabsorbed into the proximal contorted tube and henle's ansa. Proximally, K+ is passively reabsorbed with Na+ and water, while the Na+ - K+ - 2Cl light cotransporter mediates the K+ transport in the thick ascending branch of the Henle. So, the amount of K+ that reaches the level of the distal nephron (distal contorted tube and cortical collector duct) is approximately equal to the daily intake of K+. Distal secretion or reabsorption of K+ occurs in the event of an excess or loss of K+.
The cell responsible for the secretion of K+ at the end of the distal contorted tube and at the level of the cortical collector duct (DCC) is the main cell. In fact, all the adjustment of renal excretion of K+ and the total K+ balance is carried out at the level of the distal nephron. The motor force that determines the secretion of K+ is represented by a favorable electrochemical gradient along the luminal membrane of the main cell. As a result of the action of the na+, K+ - ATP-ase basolateral pump, the intracellular concentration of K+ far exceeds that of the liquid in the DCC lumen. The electric gradient is created by the electrogen reabsorption of Na+, which leads to a negative transepithelial potential difference (DPTE) in the lumen, favouring the secretion of K+.
The generation of a negative DPTE in the lumen depends on the rate of Reabsorption Na+ and the anions that accompany it (mainly Cl-). The echimoval reabsorption of Na+ and Cl- is electroneutral, while the reabsorption of Na+ in excess of Cl- is electrogenic. Na+ collection by the main cells is carried out by means of apical channels of Na+ and is determined by a low intracellular Na+ concentration, relative to that in the DCC lumen. The mechanism and regulation of the transport of Cl- at the level of the distal nephron are less clear.
Obviously, factors that interfere with both Na+ and Cl- reabsorption at the main cell will influence DPTE. Potassium secretion is regulated by two physiological stimuli: aldosterone and hyperpotasemia. Aldosterone is secreted by cells of the glomerular area of the adrenal cortex in response to increased amounts of renin and angiotensin II or hyperpotasemia. The actions of aldosterone at the level of the main cell include increasing the apical transmembrane conduction of Na+, stimulating Na+, K+- BAsolateral ATP-ase and increasing the number of k+ light channels.
The plasma concentration of K+, independent of aldosterone, may directly affect the secretion of K+. Apart from the concentration of K+ in the DCC lumen, renal losses of K+ depend on the rate of urinary flow, which in turn depends on the daily excretion of solvents. Since the amount excreted is equal to the product between concentration and volume, increased distal flow can significantly increase urinary eliminations of K+. Finally, in severe K+ deletation, the secretion of K+ is reduced and reabsorption on the Path of the H+, K+- ATP-ase in the cortical and medullary collecting ducts is increased.
Let's move on to hipposemia! Hypopotasemia, defined as a plasma concentration of K+ of less than 3.5 mmol/l, may be the result of (more) causes: decreased ingestion, K+ entry into cells or increased losses. Decreasein ingestion is rarely the only cause of K+ dout, as urinary excretion can be reduced to less than 15 mmoli/ day as a result of net reabsorption of K+ in the distal nephron. With the exception of some poor urban populations or certain cultural groups, the amount of K+ in the diet almost always exceeds the amount excreted in the urine.
However, diets low in K+ can exacerbate hipposemia secondary to increased gastrointestinal or renal loss. An unusual cause of decreased Intake of K+ is the ingestion of earth (geofagia), which binds K+ from the iron diet. This habit has been quite common in some areas or time periods. Transport of K+ to the cell may transiently decrease the plasma concentration of K+ without altering the total body's content in K+. For any of these causes, the size of the k+ concentration variations is relatively small, frequently less than 1 mmol/l. However, a combination of factors may lead to a significant decrease in the plasma concentration of K+ and may amplify the hypopotasemia caused by The Loss of K+. Alkalose, especially that of the primary increase in HCO3- in plasma (metabolic alkalose), is often associated with hypopotasemia.
This occurs as a result of K+ entry into cells or as a result of excessive renal or gastrointestinal loss of K+. Treatment of diabetic ketoacidosis with insulin can lead to hipposemia, due to stimulation of the inverse transport Na+ - H+ and (secondary) of the Na+, K+ - ATP-ase pump. Moreover, uncontrolled hyperglycaemia often leads to K+ deplation through osmotic diuresis. The release of catecholamines following stress and the administration of beta2-adrenergic agonists directly induce the entry of K+ into cells and stimulate insulin secretion in betapancreatic cells.
Hypopotasemic periodic paralysis is a rare situation, characterized by recurrent episodes of muscle weakness or paralysis. Because K+ is the main cation at the FIC level, anabolic states can cause a hypopotasemia given by the entry of K+ into the cells. This may occur with rapid cell growth observed in patients with pernicious anaemia treated with vitamin B12 or in those with neutropenia after treatment with a stimulatory factor of the granulocyto-macrophagic colonies. Massive transfusion of washed, thawed erythrocytes (E) can cause hypopotasemia, due to the fact that freezing E causes half of their K+ content to be lost during preservation.
Excessive sweating can cause K+ deletby increasing skin and kidney loss of K+. Hyperaldosteronism, secondary to the decrease in FEC volume, increases the excretion of K+ in the urine. Normally, the loss of K+ in the stool reaches up to 5-10 mmol/ day in a volume of 100 to 200 ml. Hypopotasemia following increased gastrointestinal loss may occur in patients with profuse (usually secretory) diarrhoea, vilos adenoma, VIP-oams or laxative abuse. Gastric juice losses are not among the causes of severe or moderate K+ deplation that is nevertheless commonly associated with vomiting and nasogastric aspiration.
Since the K+ concentration of gastric juice is 5-10 mmoli/ l, it would take 30-80 l vomiting to achieve a K+ deficiency of 300 to 400 mmoli, a deficiency commonly observed in these patients. In fact, hipposemia is primarily due to increased renal excretion of K+. Losses of gastric contents cause volemic doutation and metabolic alkalosis, and both stimulate kaliuresis (K - Kalium = Potassium). Hypovolemia stimulates the release of aldosterone, which increases the secretion of K+ in the main cells. In addition, the filtered amount of HCO3- exceeds the absorption capacity of the proximal contorted tube, thus increasing the distal intake of NaHCO3 which in turn increases the electrochemical gradient that favors the loss of K+ in the urine.
In general, most causes of chronic hypopotasemia are caused by renal loss of K+. This can be determined by factors that increase the concentration of K+ in the DCC lumen or increase the distal flow. As described before, the secretion of K+ in the distal nephron is determined by a negative DPTE in the lumen, which is affected by aldosterone and the rate of Reabsorption Na+ and the anions accompanying it.
Excess mineralocorticoids constantly causes hypopotasemia. Primary hypoaldosteronism is given by an impairment of aldosterone secretion by an adrenal adenoma (Conn syndrome), a carcinoma or adrenal corticosteroid hyperplasia. In a low number of patients, the disease is familial (autosomal dominant), and aldosterone levels may be decreased by taking low doses of exogenous glucocorticoid. The molecular defect responsible for hyperaldosteronism that responds to glucocorticoids is a gene rearrangement (given by a chromosomal cross).
Subsequently, mineralocorticoid is synthesized in the beamed area and regulated by corticotropin. There are several conditions associated with hyperreninemia that cause secondary hyperaldosteronism and renal loss of K+. Increased levels of renin are observed in both renovascular and malignant hypertension. The secreting renin tumors of the juxtaglomerular apparatus are a rare cause of hipposemia.
Other tumours have been criminalized in the production of renin, including renal carcinoma, ovarian carcinoma and Wilms tumor. Hyperreninemia may also occur secondary to the decrease in actual circulating arterial volume.
In the absence of increased levels of renin or aldosterone, increased secretion of K+ in the distal nephron may result in increased production of nonaldosteronic mineralocorticoids in congenital adrenal hyperplasia. Glucocorticoid-stimulated kaliuresis is not normally given by the conversion of cortisol into cortisone via 11beta-hydroxysteroid dehydrogenosis (11beta-HSDH), so its deficiency or suppression allows cortisol to bind to aldosterone receptors and lead to the apparent excess of mineralocorticoid syndrome. Drugs that inhibit the activity of 11beta-HSDH include glycyretic acid present in licorice, chewable tobacco and carbenoxolone. In Cushig syndrome, hypopotasemia may occur if 11beta-HSDH's ability to inactivate cortisol is exceeded by consistently elevated levels of glucocorticoids.
Liddle syndrome is a rare familial condition (autosomal dominant) characterized by hypertension, hypopotasemic metabolic alkalosis, renal loss of K+ and suppressed secretion of renin and aldosterone. This condition is caused by mutations within the beta subunit of the apical Na+ channels of the main cells, causing their conductivity to increase. Appropriate therapy includes Na+ restriction and administration of achlorrid, a specific inhibitor of DCC's luminal Na+ channels. The increase in the distal port of Na+ and non-resorbable anions (outside Cl-) increases the luminal negative DPTE and the secretion of K+.
Classically, this phenomenon is observed in proximal tubular acidosis (ATR) (type 2) and vomiting, associated with bicarbonate. Diabetic ketoacidosis and toluene abuse (inhaling adhesive vapours) can increase the intake of beta-hydroxybutyrate and hipurate in DCC respectively and thus increase renal losses of K+. High doses of penicillin derivatives administered to patients with volemic deplation may promote the same as an osmotic diuretic. Classical distal ATR (type 1) is associated with hypopotasemia due to increased renal loss of K+ through a lesser-known mechanism. Amphotericin B causes hypopotasemia by increasing the permeability of the distal nephron to Na+ and K+ and renal loss of K+.
Bartter syndrome is a condition characterized by hypopotasemia, metabolic alkalosis, hyperreinemic hyperaldosteronism secondary to decreased FEC volume and hyperplasia of the juxtaglomerular apparatus. Blood pressure is consistently normal, and hypomagnesemia is often present as a result of renal loss of Mg2+. The physiology of the syndrome has not yet been elucidated.
Refractory hypopotasemia with K+ administration is suggestive for Mg2+ deletation. Although the pathogenesis is unclear, hypomagnesemia can stimulate the secretion of aldosterone or decrease the distal transport of Cl-. Finally, the use and abuse of diuretics are the most common causes of K+ depletion. Carbonic anhydrase inhibitors, anse diuretics and thiazides are all kaliuretic. The degree of hypopotasemia tends to be higher in the case of diuretics with longer action and is dose dependent. The increase in renal excretion of K+ is mainly due to the increase in distal supply of solvents and secondary to hyperaldosteronism (through volemic deletation).
Clinical manifestations of K+ deletation vary greatly from patient to patient, and their severity depends on the degree of hypopotasemia. Symptoms sometimes occur at a plasma concentration of K+ below 3 mmol/ l. Fatigue, myalgia and muscle weakness of the lower limbs are common symptoms and are given by a potentiallow rest membrane (more negative). More severe hypopotasemia can cause progressive muscle weakness, hypoventilation (by affecting the respiratory muscles and possibly complete paralysis). Impairment of muscle metabolism and low hyperemic response to exertion, associated with high K+ deletation, increase the risk of rhabdomyolysis.
Smooth muscle function can also be affected and manifests as paralytic ileus. Electrocardiographic changes in hypopotasemia are given by ventricular repolarization and do not correlate well with the plasma concentration of K+. The first changes consist of flattening or inversion of T-waves, prominent U-wave, sT segment sub-levelling, and extended QU interval. Severe Dupletion of K+ may cause elongation of the PR interval, decreased amplitude and widening of QRS complexes, and an increase in the risk of ventricular arrhythmias, especially in patients with myocardial ischemia or left ventricular hypertrophy. Hypopotasemia may also predispose to digital toxicity.
Epidemiological studies link a low-K+ diet to increased prevalence of hypertension. Furthermore, in patients with essential hypertension, systemic blood pressure may be reduced by additional K+. The mechanism of the production of hypertension by K+ deletis is not clear, but may be related to an increase in distal reabsorption of NaCl. Hypopotasemia is often associated with impairment of acid-base balance related to underlying conditions. In addition, The doutlet of K+ causes intracellular acidification and increases acid excretion or production of HCO3-.
This is a consequence of increased proximal reabsorption of HCO3-, renal amyogenesis and distal secretion of H+. This contributes to the development of metabolic alkalosis, which is commonly present in patients with hypokalemia. Nephrogen insipid diabetes is quite commonly criminalized as the cause of K+ deletation and is manifested by polydipsia and polyuria. Glucose intolerance may also be associated with hypopotasemia and has been attributed to both decreased insulin secretion and peripheral insulin resistance.
From a diagnostic point of view, in most cases, the etiology of hipposemia can be determined by careful anamnesis. Abuse of diuretics and laxatives, as well as the challenge of vomiting can be difficult to identify, but you must. patients with marked leukocytosis (e.g. acute myeloid leukaemia) and normokalemia may have a low concentration of K+ due to K+ entry into leukocytes at room temperature.
This pseudohippopotasemia can be avoided by storing blood samples on ice or by rapidly separating plasma (or serum) from cells. After eliminating decreased intake and Entering K+ into cells as potential causes of hypopotasemia, examining renal function may be useful in clarifying the source of K+ loss. The appropriate response to loss of K+ is an excretion of less than 15 mmoli/ day of K+ in the urine as a result of increased reabsorption and decreased distal secretion.
Hypopotasemia with minimal renal excretion of K+ suggests that K+ has been lost either in the skin or gastrointestinal tract, or is a previous episode of vomiting or diuretic use. As described above, renal loss of K+ can be determined by factors that either increase the concentration of K+ at DCC or increase distal flow (or both). The volume of the FEC, blood pressure and associated acid-base imbalance may help to differentiate the causes of excessive renal loss of K+. A quick and simple test designed to assess the force required for the secretion of K+ is the gradient of the transtubular concentration of K+ (GCTK).
I will complete this post with the presentation of some elements related to the treatment. Therapeutic purposes are to correct the K+ deficiency and decrease continuous K+ losses. With the exception of periodic paralysis, hypopotasemia resulting from the entry of K+ into cells rarely requires additional intravenous K+, which can lead to rebound hyperpotasemia. Hypopotasemia is more definitely corrected orally.
The K+ delet gradient does not correlate well with the plasma concentration of K+. A 1 mmol/ l decrease in plasma concentration of K+ (from 4 to 3 mmol/ l) may represent a total k+ deficiency of 200 to 400 mmoli, and patients with plasma levels below 3 mmoli/ l often require an intake of 600 mmoli K+ to correct this deficiency. Furthermore, factors simulating the exit of K+ from cells (e.g. insulin deficiency in diabetic ketoacidosis) may cause an underestimation of K+ deficiency. therefore, the plasma concentration of K+ should be monitored frequently when assessing the response to treatment.
Potassium chloride is the most widely used preparation and causes a rapid correction of hypopotasemia and metabolic alkalose. Bicarbonate and K+ citrate (metabolized to HCO3-) tend to alkalize the patient and are suitable for hypopotasemia associated with chronic diarrhea or ATR.
Patients with severe hypopotasemia or those who are unable to swallow require intravenous therapy with KCl. The maximum concentration of K+ administered should not be more than 40 mmoli/ l in the peripheral veins or 60 mmoli/ l in the central veins. The rate of administration should not exceed 20 mmoli/hour, except for paralysis or malignant ventricular arrhythmias. Ideally, KCl should be administered in saline solution, as the glucose solution can initially exacerbate hypopotasemia by entering K+ into the cell, mediated by insulin. Rapid intravenous administration of K+ should be carried out with great care and requires careful observation of clinical manifestations of hypopotasemia (electrocardiogram and neuromuscular examination).
Yes, we're done!!! Tomorrow we're talking about hyperpotasemia... I hope not so much... Now I'm going to go shoot a football with the boys...
A more consistent post will follow because I want to finish as soon as possible with all this "chemistry" of electrolyte balances, especially important for the "approaches" to come.
As we announce, we will proceed to the study of potassium, starting with its balance in the body. Potassium (K) is the most important intracellular cation. The normal concentration of K+ in plasma is between 3.5 - 5 mmol/ l, while in cells it is about 150 mmol/ l. Therefore, the amount of K+ in the FEC (between 30 and 70 mmoli) represents less than 2% of the total K+ content of the body (between 2500 - 4500 mmol). The ratio of K+ concentration in FIC and FEC (normally 38:1) is the main result of resting membrane potential and is essential for normal neuromuscular functioning.
The Na+, K+ - ATP-ase basal pump actively transports K+ inside the cell and Na+ outside it in 2:3, and the passive outward diffusion of K+ is quantitatively the most important factor that generates the resting membrane potential. The activity of the Na+, K+ -ATP-ase electrogenic pump may be stimulated as a result of increased intracellular Na+ levels and may be inhibited in the case of digital toxicity or chronic conditions such as heart failure or renal failure.
K+ distribution is also affected by many other factors, including hormones, acid-base balance, osmolarity and cellular turn-over. Insulin increases the activity of the pump Na+, K+ - ATP-acivil indirectly and independently of its effects on glucose transport, leading to the entry of K+ into muscle and liver cells. In contrast, insulin deficiency causes K+ from the FIC compartment to the FEC.
Catecolamines have variable effects on the distribution of K+ - beta2 agonists - adrenergic stimulating, while alpha adrenergic agonists inhibit the collection of K+ by cells. The Na+, K+ pump - ATP-ase, as well as insulin secretion, are stimulated by beta2- adrenergic agonists. In contrast, alpha adrenergic agonists have the opposite effect. The main action of aldosterone is to increase the excretion of K+. The role of extracellular pH in the K+ balance is linked to underlying acid-base imbalances. In metabolic acidosis, 60% of the amount of H+ is buffered intracellularly.
To maintain electroneutrality, H+ ions are either accompanied by an anion or are exchanged with intracellular K+ (leading to hyperpotasemia). Organic acidosis is not commonly associated with a pH-related K+ exchange, as anions such as lactate or beta-hydroxybutyrate can be quickly picked up by the cell. K+ entry into the cell can be quickly observed in metabolic alkalose. However, this exchange is less important due to the decrease in intracellular buffering.
Primary respiratory disorders of acid-base balance cause a minimum transcellular transport of K+. In situations of hyperosmolarity, K+ diffuses into the extracellular space together with the water that thus constitutes the "pulling solvent". The concentration gradient, which favours the passage of K+ into the extracellular space is also increased as a result of water loss from fic. Tissue destruction or catabolism causes the release of intracellular K+, while in the formation of new cells K+ is used from the FEC level.
Finally, moderate or increased exercise may be associated with the release of K+ from the muscles, leading to glycogenolosis and local vasodilation. This is normally transient, but may affect the plasma concentration of K+ if the patient repeatedly squeezes and loosens the fist before the venous puncture.
Ingestion of K+ in an average Western diet is 40 to 120 mmoli/ day or about 1 mmol/ kg/ day, 90% of which is absorbed through the gastrointestinal tract.
Maintaining a balance requires a correlation between ingestion and secretion of K+. Initially, extrarenal adaptive mechanisms and then urinary excretion prevent the doubling of the plasma concentration of K+, which could occur if the entire amount of K+ in the diet remained in the FEC space. Immediately after the meal, the vast majority of the absorbed K+ enters the cells as a result of the initial increase in the plasma concentration of K+, the process being favored by the release of insulin and the basal levels of catecholamines.
An excess of K+ is excreted through urine. The regulation of intestinal absorption of K+ is not fully understood. The amount of Lost K+ caught stool can increase from 10 to 50 or 60% (from daily intake) in chronic renal failure. In addition, colonic secretion of K+ is stimulated in patients with large amounts of diarrhoea and can lead to severe K+ discharge.
Excretion of K+ occurs mainly through renal excretion which is the main route of removing excess K+ from diet or other sources. The amount of K+ filtered is 10-20 times the K+ content of the FEC. 90% of the filtered K+ is reabsorbed into the proximal contorted tube and henle's ansa. Proximally, K+ is passively reabsorbed with Na+ and water, while the Na+ - K+ - 2Cl light cotransporter mediates the K+ transport in the thick ascending branch of the Henle. So, the amount of K+ that reaches the level of the distal nephron (distal contorted tube and cortical collector duct) is approximately equal to the daily intake of K+. Distal secretion or reabsorption of K+ occurs in the event of an excess or loss of K+.
The cell responsible for the secretion of K+ at the end of the distal contorted tube and at the level of the cortical collector duct (DCC) is the main cell. In fact, all the adjustment of renal excretion of K+ and the total K+ balance is carried out at the level of the distal nephron. The motor force that determines the secretion of K+ is represented by a favorable electrochemical gradient along the luminal membrane of the main cell. As a result of the action of the na+, K+ - ATP-ase basolateral pump, the intracellular concentration of K+ far exceeds that of the liquid in the DCC lumen. The electric gradient is created by the electrogen reabsorption of Na+, which leads to a negative transepithelial potential difference (DPTE) in the lumen, favouring the secretion of K+.
The generation of a negative DPTE in the lumen depends on the rate of Reabsorption Na+ and the anions that accompany it (mainly Cl-). The echimoval reabsorption of Na+ and Cl- is electroneutral, while the reabsorption of Na+ in excess of Cl- is electrogenic. Na+ collection by the main cells is carried out by means of apical channels of Na+ and is determined by a low intracellular Na+ concentration, relative to that in the DCC lumen. The mechanism and regulation of the transport of Cl- at the level of the distal nephron are less clear.
Obviously, factors that interfere with both Na+ and Cl- reabsorption at the main cell will influence DPTE. Potassium secretion is regulated by two physiological stimuli: aldosterone and hyperpotasemia. Aldosterone is secreted by cells of the glomerular area of the adrenal cortex in response to increased amounts of renin and angiotensin II or hyperpotasemia. The actions of aldosterone at the level of the main cell include increasing the apical transmembrane conduction of Na+, stimulating Na+, K+- BAsolateral ATP-ase and increasing the number of k+ light channels.
The plasma concentration of K+, independent of aldosterone, may directly affect the secretion of K+. Apart from the concentration of K+ in the DCC lumen, renal losses of K+ depend on the rate of urinary flow, which in turn depends on the daily excretion of solvents. Since the amount excreted is equal to the product between concentration and volume, increased distal flow can significantly increase urinary eliminations of K+. Finally, in severe K+ deletation, the secretion of K+ is reduced and reabsorption on the Path of the H+, K+- ATP-ase in the cortical and medullary collecting ducts is increased.
Let's move on to hipposemia! Hypopotasemia, defined as a plasma concentration of K+ of less than 3.5 mmol/l, may be the result of (more) causes: decreased ingestion, K+ entry into cells or increased losses. Decreasein ingestion is rarely the only cause of K+ dout, as urinary excretion can be reduced to less than 15 mmoli/ day as a result of net reabsorption of K+ in the distal nephron. With the exception of some poor urban populations or certain cultural groups, the amount of K+ in the diet almost always exceeds the amount excreted in the urine.
However, diets low in K+ can exacerbate hipposemia secondary to increased gastrointestinal or renal loss. An unusual cause of decreased Intake of K+ is the ingestion of earth (geofagia), which binds K+ from the iron diet. This habit has been quite common in some areas or time periods. Transport of K+ to the cell may transiently decrease the plasma concentration of K+ without altering the total body's content in K+. For any of these causes, the size of the k+ concentration variations is relatively small, frequently less than 1 mmol/l. However, a combination of factors may lead to a significant decrease in the plasma concentration of K+ and may amplify the hypopotasemia caused by The Loss of K+. Alkalose, especially that of the primary increase in HCO3- in plasma (metabolic alkalose), is often associated with hypopotasemia.
This occurs as a result of K+ entry into cells or as a result of excessive renal or gastrointestinal loss of K+. Treatment of diabetic ketoacidosis with insulin can lead to hipposemia, due to stimulation of the inverse transport Na+ - H+ and (secondary) of the Na+, K+ - ATP-ase pump. Moreover, uncontrolled hyperglycaemia often leads to K+ deplation through osmotic diuresis. The release of catecholamines following stress and the administration of beta2-adrenergic agonists directly induce the entry of K+ into cells and stimulate insulin secretion in betapancreatic cells.
Hypopotasemic periodic paralysis is a rare situation, characterized by recurrent episodes of muscle weakness or paralysis. Because K+ is the main cation at the FIC level, anabolic states can cause a hypopotasemia given by the entry of K+ into the cells. This may occur with rapid cell growth observed in patients with pernicious anaemia treated with vitamin B12 or in those with neutropenia after treatment with a stimulatory factor of the granulocyto-macrophagic colonies. Massive transfusion of washed, thawed erythrocytes (E) can cause hypopotasemia, due to the fact that freezing E causes half of their K+ content to be lost during preservation.
Excessive sweating can cause K+ deletby increasing skin and kidney loss of K+. Hyperaldosteronism, secondary to the decrease in FEC volume, increases the excretion of K+ in the urine. Normally, the loss of K+ in the stool reaches up to 5-10 mmol/ day in a volume of 100 to 200 ml. Hypopotasemia following increased gastrointestinal loss may occur in patients with profuse (usually secretory) diarrhoea, vilos adenoma, VIP-oams or laxative abuse. Gastric juice losses are not among the causes of severe or moderate K+ deplation that is nevertheless commonly associated with vomiting and nasogastric aspiration.
Since the K+ concentration of gastric juice is 5-10 mmoli/ l, it would take 30-80 l vomiting to achieve a K+ deficiency of 300 to 400 mmoli, a deficiency commonly observed in these patients. In fact, hipposemia is primarily due to increased renal excretion of K+. Losses of gastric contents cause volemic doutation and metabolic alkalosis, and both stimulate kaliuresis (K - Kalium = Potassium). Hypovolemia stimulates the release of aldosterone, which increases the secretion of K+ in the main cells. In addition, the filtered amount of HCO3- exceeds the absorption capacity of the proximal contorted tube, thus increasing the distal intake of NaHCO3 which in turn increases the electrochemical gradient that favors the loss of K+ in the urine.
In general, most causes of chronic hypopotasemia are caused by renal loss of K+. This can be determined by factors that increase the concentration of K+ in the DCC lumen or increase the distal flow. As described before, the secretion of K+ in the distal nephron is determined by a negative DPTE in the lumen, which is affected by aldosterone and the rate of Reabsorption Na+ and the anions accompanying it.
Excess mineralocorticoids constantly causes hypopotasemia. Primary hypoaldosteronism is given by an impairment of aldosterone secretion by an adrenal adenoma (Conn syndrome), a carcinoma or adrenal corticosteroid hyperplasia. In a low number of patients, the disease is familial (autosomal dominant), and aldosterone levels may be decreased by taking low doses of exogenous glucocorticoid. The molecular defect responsible for hyperaldosteronism that responds to glucocorticoids is a gene rearrangement (given by a chromosomal cross).
Subsequently, mineralocorticoid is synthesized in the beamed area and regulated by corticotropin. There are several conditions associated with hyperreninemia that cause secondary hyperaldosteronism and renal loss of K+. Increased levels of renin are observed in both renovascular and malignant hypertension. The secreting renin tumors of the juxtaglomerular apparatus are a rare cause of hipposemia.
Other tumours have been criminalized in the production of renin, including renal carcinoma, ovarian carcinoma and Wilms tumor. Hyperreninemia may also occur secondary to the decrease in actual circulating arterial volume.
In the absence of increased levels of renin or aldosterone, increased secretion of K+ in the distal nephron may result in increased production of nonaldosteronic mineralocorticoids in congenital adrenal hyperplasia. Glucocorticoid-stimulated kaliuresis is not normally given by the conversion of cortisol into cortisone via 11beta-hydroxysteroid dehydrogenosis (11beta-HSDH), so its deficiency or suppression allows cortisol to bind to aldosterone receptors and lead to the apparent excess of mineralocorticoid syndrome. Drugs that inhibit the activity of 11beta-HSDH include glycyretic acid present in licorice, chewable tobacco and carbenoxolone. In Cushig syndrome, hypopotasemia may occur if 11beta-HSDH's ability to inactivate cortisol is exceeded by consistently elevated levels of glucocorticoids.
Liddle syndrome is a rare familial condition (autosomal dominant) characterized by hypertension, hypopotasemic metabolic alkalosis, renal loss of K+ and suppressed secretion of renin and aldosterone. This condition is caused by mutations within the beta subunit of the apical Na+ channels of the main cells, causing their conductivity to increase. Appropriate therapy includes Na+ restriction and administration of achlorrid, a specific inhibitor of DCC's luminal Na+ channels. The increase in the distal port of Na+ and non-resorbable anions (outside Cl-) increases the luminal negative DPTE and the secretion of K+.
Classically, this phenomenon is observed in proximal tubular acidosis (ATR) (type 2) and vomiting, associated with bicarbonate. Diabetic ketoacidosis and toluene abuse (inhaling adhesive vapours) can increase the intake of beta-hydroxybutyrate and hipurate in DCC respectively and thus increase renal losses of K+. High doses of penicillin derivatives administered to patients with volemic deplation may promote the same as an osmotic diuretic. Classical distal ATR (type 1) is associated with hypopotasemia due to increased renal loss of K+ through a lesser-known mechanism. Amphotericin B causes hypopotasemia by increasing the permeability of the distal nephron to Na+ and K+ and renal loss of K+.
Bartter syndrome is a condition characterized by hypopotasemia, metabolic alkalosis, hyperreinemic hyperaldosteronism secondary to decreased FEC volume and hyperplasia of the juxtaglomerular apparatus. Blood pressure is consistently normal, and hypomagnesemia is often present as a result of renal loss of Mg2+. The physiology of the syndrome has not yet been elucidated.
Refractory hypopotasemia with K+ administration is suggestive for Mg2+ deletation. Although the pathogenesis is unclear, hypomagnesemia can stimulate the secretion of aldosterone or decrease the distal transport of Cl-. Finally, the use and abuse of diuretics are the most common causes of K+ depletion. Carbonic anhydrase inhibitors, anse diuretics and thiazides are all kaliuretic. The degree of hypopotasemia tends to be higher in the case of diuretics with longer action and is dose dependent. The increase in renal excretion of K+ is mainly due to the increase in distal supply of solvents and secondary to hyperaldosteronism (through volemic deletation).
Clinical manifestations of K+ deletation vary greatly from patient to patient, and their severity depends on the degree of hypopotasemia. Symptoms sometimes occur at a plasma concentration of K+ below 3 mmol/ l. Fatigue, myalgia and muscle weakness of the lower limbs are common symptoms and are given by a potentiallow rest membrane (more negative). More severe hypopotasemia can cause progressive muscle weakness, hypoventilation (by affecting the respiratory muscles and possibly complete paralysis). Impairment of muscle metabolism and low hyperemic response to exertion, associated with high K+ deletation, increase the risk of rhabdomyolysis.
Smooth muscle function can also be affected and manifests as paralytic ileus. Electrocardiographic changes in hypopotasemia are given by ventricular repolarization and do not correlate well with the plasma concentration of K+. The first changes consist of flattening or inversion of T-waves, prominent U-wave, sT segment sub-levelling, and extended QU interval. Severe Dupletion of K+ may cause elongation of the PR interval, decreased amplitude and widening of QRS complexes, and an increase in the risk of ventricular arrhythmias, especially in patients with myocardial ischemia or left ventricular hypertrophy. Hypopotasemia may also predispose to digital toxicity.
Epidemiological studies link a low-K+ diet to increased prevalence of hypertension. Furthermore, in patients with essential hypertension, systemic blood pressure may be reduced by additional K+. The mechanism of the production of hypertension by K+ deletis is not clear, but may be related to an increase in distal reabsorption of NaCl. Hypopotasemia is often associated with impairment of acid-base balance related to underlying conditions. In addition, The doutlet of K+ causes intracellular acidification and increases acid excretion or production of HCO3-.
This is a consequence of increased proximal reabsorption of HCO3-, renal amyogenesis and distal secretion of H+. This contributes to the development of metabolic alkalosis, which is commonly present in patients with hypokalemia. Nephrogen insipid diabetes is quite commonly criminalized as the cause of K+ deletation and is manifested by polydipsia and polyuria. Glucose intolerance may also be associated with hypopotasemia and has been attributed to both decreased insulin secretion and peripheral insulin resistance.
From a diagnostic point of view, in most cases, the etiology of hipposemia can be determined by careful anamnesis. Abuse of diuretics and laxatives, as well as the challenge of vomiting can be difficult to identify, but you must. patients with marked leukocytosis (e.g. acute myeloid leukaemia) and normokalemia may have a low concentration of K+ due to K+ entry into leukocytes at room temperature.
This pseudohippopotasemia can be avoided by storing blood samples on ice or by rapidly separating plasma (or serum) from cells. After eliminating decreased intake and Entering K+ into cells as potential causes of hypopotasemia, examining renal function may be useful in clarifying the source of K+ loss. The appropriate response to loss of K+ is an excretion of less than 15 mmoli/ day of K+ in the urine as a result of increased reabsorption and decreased distal secretion.
Hypopotasemia with minimal renal excretion of K+ suggests that K+ has been lost either in the skin or gastrointestinal tract, or is a previous episode of vomiting or diuretic use. As described above, renal loss of K+ can be determined by factors that either increase the concentration of K+ at DCC or increase distal flow (or both). The volume of the FEC, blood pressure and associated acid-base imbalance may help to differentiate the causes of excessive renal loss of K+. A quick and simple test designed to assess the force required for the secretion of K+ is the gradient of the transtubular concentration of K+ (GCTK).
I will complete this post with the presentation of some elements related to the treatment. Therapeutic purposes are to correct the K+ deficiency and decrease continuous K+ losses. With the exception of periodic paralysis, hypopotasemia resulting from the entry of K+ into cells rarely requires additional intravenous K+, which can lead to rebound hyperpotasemia. Hypopotasemia is more definitely corrected orally.
The K+ delet gradient does not correlate well with the plasma concentration of K+. A 1 mmol/ l decrease in plasma concentration of K+ (from 4 to 3 mmol/ l) may represent a total k+ deficiency of 200 to 400 mmoli, and patients with plasma levels below 3 mmoli/ l often require an intake of 600 mmoli K+ to correct this deficiency. Furthermore, factors simulating the exit of K+ from cells (e.g. insulin deficiency in diabetic ketoacidosis) may cause an underestimation of K+ deficiency. therefore, the plasma concentration of K+ should be monitored frequently when assessing the response to treatment.
Potassium chloride is the most widely used preparation and causes a rapid correction of hypopotasemia and metabolic alkalose. Bicarbonate and K+ citrate (metabolized to HCO3-) tend to alkalize the patient and are suitable for hypopotasemia associated with chronic diarrhea or ATR.
Patients with severe hypopotasemia or those who are unable to swallow require intravenous therapy with KCl. The maximum concentration of K+ administered should not be more than 40 mmoli/ l in the peripheral veins or 60 mmoli/ l in the central veins. The rate of administration should not exceed 20 mmoli/hour, except for paralysis or malignant ventricular arrhythmias. Ideally, KCl should be administered in saline solution, as the glucose solution can initially exacerbate hypopotasemia by entering K+ into the cell, mediated by insulin. Rapid intravenous administration of K+ should be carried out with great care and requires careful observation of clinical manifestations of hypopotasemia (electrocardiogram and neuromuscular examination).
Yes, we're done!!! Tomorrow we're talking about hyperpotasemia... I hope not so much... Now I'm going to go shoot a football with the boys...
Have a good day, full of
understanding, love and gratitude!
Dorin, Merticaru