Hyperkalemia pathophysiology: Difference between revisions

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{{CMG}}; '''Associate Editor(s)-In-Chief:''' [[Jogeet Singh Sekhon]]
{{CMG}}; '''Associate Editor(s)-In-Chief:''' [[Jogeet Singh Sekhon]]
==Overview==
==Overview==
Potassium is the most abundant [[intracellular]] [[cation]] and is critically important for many physiologic processes. The normal range of potassium in blood is 3.5-5.1mEq/L. [[.Hyperkalemia|Hyperkalemia]] develops when the level of potassium exceeds 5.5 meq/L in blood which can be due to an increase in intake of potassium, excessive production as seen in tissue breakdown, ineffective elimination of potassium or some drugs. The [[potassium]] levels in the body are highly regulated mainly by renal excretion. The gut excretes a minimal amount of dietary potassium (approximately 10%). Hyperkalemia is very common in patients with [[Chronic renal failure|chronic kidney disease]] as potassium is not effectively excreted from the body. Potassium is involved in maintaining transmembrane potential of the cells, so imbalance in potassium levels can lead to disruption of cell membrane potentials and can cause hyperexcitablity leading to fatal [[Cardiac arrhythmia|cardiac arrhythmias]] and may affect the nervous system.
[[Potassium]] is the most abundant [[intracellular]] [[cation]] and is critically important for many [[physiologic]] processes. The normal range of [[potassium]] in blood is 3.5-5.1mEq/L. Hyperkalemia develops when the level of [[potassium]] exceeds 5.5 mEq/L in blood which can be due to an increase in intake of [[potassium]], excessive production as seen in tissue breakdown, transcellular shift of [[potassium]], ineffective elimination of [[potassium]] or due to some drugs. The [[potassium]] levels in the body are highly regulated mainly by [[renal]] excretion. The [[gut]] excretes a minimal amount of [[dietary]] [[potassium]] (approximately 10%). Hyperkalemia is very common in [[patients]] with [[Chronic renal failure|chronic kidney disease]] as [[potassium]] is not effectively excreted from the body. [[Potassium]] is involved in maintaining [[transmembrane potential]] of the cells, so imbalance in [[potassium]] levels can lead to disruption of [[cell membrane]] [[Potential|potentials]] and can cause hyperexcitablity leading to fatal [[Cardiac arrhythmia|cardiac arrhythmias]] and may affect the [[nervous system]].


==Pathophysiology==
==Pathophysiology==
====Physiological role of potassium====
====Physiological role of potassium====
Potassium is the major [[intracellular cation]] and sodium is the major extracellular cation. Almost all cells possess an Na<sup>+</sup>-K<sup>+</sup>-ATPase, which pumps Na<sup>+</sup> out of the cell and K<sup>+</sup> into the cell and leads to a K<sup>+</sup> gradient across the cell membrane (K<sup>+</sup>in>K<sup>+</sup>out) that is partially responsible for maintaining the [[potential difference]] across the membrane. This potential difference called the [[transmembrane potential]] is responsible for the excitability of the cells.<ref name="pmid11095656">{{cite journal| author=De Nicola L, Bellizzi V, Minutolo R, Cioffi M, Giannattasio P, Terracciano V et al.| title=Effect of dialysate sodium concentration on interdialytic increase of potassium. | journal=J Am Soc Nephrol | year= 2000 | volume= 11 | issue= 12 | pages= 2337-43 | pmid=11095656 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11095656  }} </ref>
*[[Potassium]] is the major intracellular cation and [[sodium]] is the major [[extracellular]] cation <ref name="pmid9612319">{{cite journal| author=Giebisch G| title=Renal potassium transport: mechanisms and regulation. | journal=Am J Physiol | year= 1998 | volume= 274 | issue= 5 Pt 2 | pages= F817-33 | pmid=9612319 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9612319  }} </ref>
 
* Almost all [[cells]] possess an Na<sup>+</sup>-K<sup>+</sup>-ATPase, which pumps Na<sup>+</sup> out of the cell and K<sup>+</sup> into the cell and leads to a K<sup>+</sup> gradient across the [[cell membrane]] (K<sup>+</sup>in>K<sup>+</sup>out) that is partially responsible for maintaining the [[potential difference]] across the membrane.
* This potential difference called the [[transmembrane potential]] is responsible for the excitability of the cells <ref name="pmid11095656">{{cite journal| author=De Nicola L, Bellizzi V, Minutolo R, Cioffi M, Giannattasio P, Terracciano V et al.| title=Effect of dialysate sodium concentration on interdialytic increase of potassium. | journal=J Am Soc Nephrol | year= 2000 | volume= 11 | issue= 12 | pages= 2337-43 | pmid=11095656 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11095656  }} </ref>
[[File:Scheme sodium-potassium pump-it svg.png|center|thumb|400px|Sodium-Potassium-ATPase Pump Source: Courtesy of Mariana Ruiz Villarreal, via Wikimedia commons<ref>{{cite web |url=https://commons.wikimedia.org/wiki/File:Scheme_sodium-potassium_pump-it.svg |title=File:Scheme sodium-potassium pump-it.svg - Wikimedia Commons |format= |work= |accessdate=}}</ref>]]
[[File:Scheme sodium-potassium pump-it svg.png|center|thumb|400px|Sodium-Potassium-ATPase Pump Source: Courtesy of Mariana Ruiz Villarreal, via Wikimedia commons<ref>{{cite web |url=https://commons.wikimedia.org/wiki/File:Scheme_sodium-potassium_pump-it.svg |title=File:Scheme sodium-potassium pump-it.svg - Wikimedia Commons |format= |work= |accessdate=}}</ref>]]
=====Factors affecting transcellular shift of potassium=====
=====Factors affecting transcellular shift of potassium=====
The distribution of potassium inside and outside the cells is maintained by various pumps, [[osmolarity]], pH and the hormones including [[insulin]], [[aldosterone]], [[catecholamines]] and [[Prostaglandin|prostaglandins]].
The distribution of [[potassium]] inside and outside the [[cells]] is maintained by various pumps, [[osmolarity]], [[pH]] and the [[hormones]] including [[insulin]], [[aldosterone]], [[catecholamines]] and [[Prostaglandin|prostaglandins]].
* Insulin regulates potassium uptake into the cells through GLUT receptors on the cell membranes by increasing the activity of Na+-K+-ATPase pump.<ref name="pmid28585859">{{cite journal| author=Lesko LJ, Offman E, Brew CT, Garza D, Benton W, Mayo MR et al.| title=Evaluation of the Potential for Drug Interactions With Patiromer in Healthy Volunteers. | journal=J Cardiovasc Pharmacol Ther | year= 2017 | volume= 22 | issue= 5 | pages= 434-446 | pmid=28585859 | doi=10.1177/1074248417691135 | pmc=5555446 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28585859  }} </ref>  
*[[Insulin]] regulates [[potassium]] uptake into the [[cells]] through GLUT [[receptors]] on the [[cell membranes]] by increasing the activity of Na<sup>+</sup>-K<sup>+</sup>-ATPase pump<ref name="pmid28585859">{{cite journal| author=Lesko LJ, Offman E, Brew CT, Garza D, Benton W, Mayo MR et al.| title=Evaluation of the Potential for Drug Interactions With Patiromer in Healthy Volunteers. | journal=J Cardiovasc Pharmacol Ther | year= 2017 | volume= 22 | issue= 5 | pages= 434-446 | pmid=28585859 | doi=10.1177/1074248417691135 | pmc=5555446 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28585859  }} </ref>


* [[Catecholamine|Catecholamines]] regulate potassium uptake into the cells through [[β2-Receptor]]–induced stimulation of Na<sup>+-</sup>K<sup>+-</sup>ATPase pump.
* [[Catecholamine|Catecholamines]] regulate [[potassium]] uptake into the [[cells]] through β2-Receptor–induced stimulation of Na<sup>+</sup>K<sup>+</sup>ATPase pump
* Increased [[osmolarity]] as in [[hyperglycemia]] causes water efflux from the cells that drags potassium along.
* Increased [[osmolarity]] as in [[hyperglycemia]] causes [[water]] [[efflux]] from the [[cells]] that drags [[potassium]] along.
* In [[acidosis]], the decreased extracellular pH decreases the rate of Na+-H<sup>+</sup> exchange (NHE1) and inhibit the inward rate of Na<sup>+-</sup>3HCO3 cotransport,thus decreasing intracellular Na<sup>+</sup> levels which in turn decreases the activity of Na<sup>+-</sup>K<sup>+</sup>-ATPase pump and decreasing intracellular K<sup>+</sup> levels.
* In [[acidosis]], the decreased [[extracellular]] pH decreases the rate of Na+-H<sup>+</sup> exchange (NHE1) and inhibit the inward rate of [[sodium bicarbonate]] (NaHCO3) cotransport,thus decreasing [[intracellular]] Na<sup>+</sup> levels which in turn decreases the activity of Na<sup>+-</sup>K<sup>+</sup>-[[ATPase]] pump and decreasing intracellular K<sup>+</sup> levels.
* In [[alkalosis]], the increased extracellular pH increases the rate of Na<sup>+</sup>-H<sup>+</sup> exchange (NHE1) and increases the inward rate of Na<sup>+</sup>-3HCO3 cotransport,thus increasing intracellular Na<sup>+</sup> levels which in turn increases the activity of Na<sup>+-</sup>K<sup>+-</sup>ATPase pump and increasing intracellular K<sup>+</sup> levels.
* In [[alkalosis]], the increased [[extracellular]] pH increases the rate of NHE1 and increases the inward rate of NaHCO3 cotransport, Thus increasing [[intracellular]] Na<sup>+</sup> levels which in turn increases the activity of Na<sup>+-</sup>K<sup>+-</sup>ATPase pump and increasing intracellular K<sup>+</sup> levels.


====Role of kidneys====  
====Role of kidneys====
The source of potassium to the body is diet. The potassium levels in the body are dependent on dietary intake, tissue breakdown, gastrointestinal absorption and losses and most important is renal regulation via absorption and secretion. Kidneys play an important role in keeping the balance of potassium.
* The [[potassium]] levels in the body are dependent on dietary intake, tissue breakdown, gastrointestinal absorption and losses and most important is renal regulation via absorption and secretion. Kidneys play an important role in keeping the balance of potassium.
* At the [[glomerulus]], potassium is freely filtered and then largely reabsorbed in the [[proximal tubule]] and thick ascending loop of Henle (>60 % of filtered potassium).  
 
* The cortical collecting duct receives 10–15% of filtered potassium and constitutes the kidney’s major site of potassium excretion.
* At the [[glomerulus]], [[potassium]] is freely filtered and then largely reabsorbed in the [[proximal tubule]] and thick ascending loop of Henle (>60 % of filtered [[potassium]]).
* Potassium excretion at the cortical collecting duct depends on the amount of sodium delivered there and the activity of [[Aldosterone|aldosterone.]] It does so by the following ways.<ref name="pmid18839206">{{cite journal| author=Wang WH, Giebisch G| title=Regulation of potassium (K) handling in the renal collecting duct. | journal=Pflugers Arch | year= 2009 | volume= 458 | issue= 1 | pages= 157-68 | pmid=18839206 | doi=10.1007/s00424-008-0593-3 | pmc=2730119 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18839206  }} </ref> <ref name="pmid21170894">{{cite journal| author=Giebisch GH, Wang WH| title=Potassium transport--an update. | journal=J Nephrol | year= 2010 | volume= 23 Suppl 16 | issue=  | pages= S97-104 | pmid=21170894 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21170894  }} </ref>
* The cortical [[collecting duct]] receives 10–15% of filtered [[potassium]] and constitutes the [[Kidney|kidney’s]] major site of [[potassium]] excretion.
** Increases intracellular K<sup>+</sup> concentration by stimulating the activity of the Na<sup>+-</sup>K<sup>+-</sup>ATPase in the basolateral membrane.
* Potassium excretion at the cortical collecting duct depends on the amount of sodium delivered there and the activity of [[Aldosterone|aldosterone.]] It does so by the following ways.<ref name="pmid18839206">{{cite journal| author=Wang WH, Giebisch G| title=Regulation of potassium (K) handling in the renal collecting duct. | journal=Pflugers Arch | year= 2009 | volume= 458 | issue= 1 | pages= 157-68 | pmid=18839206 | doi=10.1007/s00424-008-0593-3 | pmc=2730119 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18839206  }} </ref><ref name="pmid21170894">{{cite journal| author=Giebisch GH, Wang WH| title=Potassium transport--an update. | journal=J Nephrol | year= 2010 | volume= 23 Suppl 16 | issue=  | pages= S97-104 | pmid=21170894 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21170894 }} </ref><ref name="pmid19036846">{{cite journal| author=Frindt G, Shah A, Edvinsson J, Palmer LG| title=Dietary K regulates ROMK channels in connecting tubule and cortical collecting duct of rat kidney. | journal=Am J Physiol Renal Physiol | year= 2009 | volume= 296 | issue= 2 | pages= F347-54 | pmid=19036846 | doi=10.1152/ajprenal.90527.2008 | pmc=2643862 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19036846 }} </ref>
** Increases intracellular K<sup>+</sup> concentration by stimulating the activity of the Na<sup>+-</sup>K<sup>+-</sup>ATPase at the basolateral membrane.
** Stimulates Na<sup>+</sup> reabsorption across the luminal membrane, which increases the electronegativity of the lumen, thereby increasing the electrical gradient favoring K<sup>+</sup> secretion. If the rate of delivery of sodium and water is very high in the [[Distal convoluted tubule|distal tubules]] then it will cause more Na<sup>+</sup> reabsorption and more K<sup>+</sup> secretion.
** Stimulates Na<sup>+</sup> reabsorption across the luminal membrane, which increases the electronegativity of the lumen, thereby increasing the electrical gradient favoring K<sup>+</sup> secretion. If the rate of delivery of sodium and water is very high in the [[Distal convoluted tubule|distal tubules]] then it will cause more Na<sup>+</sup> reabsorption and more K<sup>+</sup> secretion.
* Has a direct effect on the luminal membrane to increase K<sup>+</sup> permeability.  
* Has a direct effect on the luminal membrane to increase K<sup>+</sup> permeability.<ref name="pmid7836937">{{cite journal| author=Palmer LG, Antonian L, Frindt G| title=Regulation of apical K and Na channels and Na/K pumps in rat cortical collecting tubule by dietary K. | journal=J Gen Physiol | year= 1994 | volume= 104 | issue= 4 | pages= 693-710 | pmid=7836937 | doi= | pmc=2229228 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7836937  }} </ref>
Alteration in the levels of potassium occur due to disruption in the above mentioned mechanisms that regulate potassium homeostasis.
 
* Alteration in the levels of potassium occur due to disruption in the above mentioned mechanisms that regulate potassium homeostasis.


===Pathogenesis===
===Pathogenesis===
Hyperkalemia means excessive potassium in the blood(>5.1 meq/L). It can result from excessive potassium intake, increased tissue breakdown, increased transcellular shift or impaired excretion from the body <ref name="pmid10564246">{{cite journal| author=Palmer LG, Frindt G| title=Regulation of apical K channels in rat cortical collecting tubule during changes in dietary K intake. | journal=Am J Physiol | year= 1999 | volume= 277 | issue= 5 Pt 2 | pages= F805-12 | pmid=10564246 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10564246  }} </ref>.
* Hyperkalemia means excessive potassium in the blood(>5.1 meq/L).
*Increased uptake-the only source of potassium to our body is by diet. If potassium rich diet is consumed or given parenterally, it can lead to hyperkalemia. However, in individuals with normal renal function, potassium levels are regulated and excess potassium is excreted.
* It can result from excessive potassium intake, increased tissue breakdown, increased transcellular shift or impaired excretion from the body <ref name="pmid10564246">{{cite journal| author=Palmer LG, Frindt G| title=Regulation of apical K channels in rat cortical collecting tubule during changes in dietary K intake. | journal=Am J Physiol | year= 1999 | volume= 277 | issue= 5 Pt 2 | pages= F805-12 | pmid=10564246 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10564246  }} </ref>.


*Transcellular shift:
====== Increased uptake ======
**Change in extracellular pH-decrease in pH as in mineral [[acidosis]] leads to increased shift of potassium from intracellular to extracellular space.
*The only source of potassium to our body is by diet. If potassium rich diet is consumed or given parenterally, it can lead to hyperkalemia. However, in individuals with normal renal function, potassium levels are regulated and excess potassium is excreted
**Decrease in insulin as in [[diabetes mellitus]] can lead to increased extracellular accumulation of potassium.
====== Transcellular shift ======
**Increase in osmolarity as in [[hyperglycemia]] will cause extracellular shift of potassium.
*Change in extracellular pH-decrease in pH as in mineral [[acidosis]] leads to increased shift of potassium from intracellular to extracellular space.
**Decreased catecholamines or reduced function as with [[beta blockers]] use will lead to decreased uptake by cells resulting in extracellular accumulation of potassium.
*Decrease in insulin as in [[diabetes mellitus]], can lead to increased extracellular accumulation of potassium.
*Tissue breakdown:
*Increase in osmolarity as in [[hyperglycemia]], will cause extracellular shift of potassium.
**Increased tissue breakdown can occur as in [[rhabdomylosis]], burns, [[Hemolytic anemia|haemolytic]] conditions or [[chemotherapy]] induced tissue breakdown.
*Decreased catecholamines or reduced function as with [[beta blockers]] use will lead to decreased uptake by cells resulting in extracellular accumulation of potassium.
**[[Pseudohyperkalemia]] referred to as increased serum potassium levels but plasma potassium levels are within range.This usually occurs invitro while collecting a blood sample, [[thrombocytosis]] or in [[Myeloproliferative neoplasm|myeloproliferative diseases]].
 
*Impaired excretion-potassium levels in body are regulated by the kidneys. Any impairment in the excretion mechanisms can result in hyperkalemia.
====== Tissue breakdown ======
*Increased tissue breakdown can occur as in [[rhabdomylosis]], burns, [[Hemolytic anemia|haemolytic]] conditions or [[chemotherapy]] induced tissue breakdown.<ref name="pmid2729129">{{cite journal| author=Thomson A, Kelly DT| title=Exercise stress-induced changes in systemic arterial potassium in angina pectoris. | journal=Am J Cardiol | year= 1989 | volume= 63 | issue= 20 | pages= 1435-40 | pmid=2729129 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2729129  }} </ref>
 
*[[Pseudohyperkalemia]] referred to as increased serum potassium levels but plasma potassium levels are within range.This usually occurs invitro while collecting a blood sample, [[thrombocytosis]] or in [[Myeloproliferative neoplasm|myeloproliferative diseases]].<ref name="pmid3400632">{{cite journal| author=Graber M, Subramani K, Corish D, Schwab A| title=Thrombocytosis elevates serum potassium. | journal=Am J Kidney Dis | year= 1988 | volume= 12 | issue= 2 | pages= 116-20 | pmid=3400632 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3400632  }} </ref>
.
 
====== Impaired excretion ======
*Potassium levels in body are regulated by the kidneys. Any impairment in the excretion mechanisms can result in hyperkalemia.
*Reduced [[Glomerular filtration rate|GFR]](<15ml/min) results in decreased urine flow and hence decreased sodium and water delivery to the distal tubules resulting in decreased secretion of potassium.
*Reduced [[Glomerular filtration rate|GFR]](<15ml/min) results in decreased urine flow and hence decreased sodium and water delivery to the distal tubules resulting in decreased secretion of potassium.
*Decrease in the levels of aldosterone as in primary [[hypoaldosteronism]] and secondary hypoaldosteronism results in impaired excretion of potassium.
*Decrease in the levels of aldosterone as in primary [[hypoaldosteronism]] and secondary hypoaldosteronism results in impaired excretion of potassium.
*[[Pseudohypoaldostrenism]]- the levels of aldosterone are within normal limits but there is resistance to aldosterone in the kidneys and is not able to exert its function.
*Pseudohypoaldostrenism- the levels of [[aldosterone]] are within normal limits but there is resistance to aldosterone in the kidneys and is not able to exert its function.
*Chronic kidney diseases- the overall renal function is impaired resulting in decreased secretion of potassium as in various [[Nephropathy|nephropathies.]]
*[[Chronic kidney disease]]- the overall renal function is impaired resulting in decreased secretion of potassium as in various [[Nephropathy|nephropathies.]]
*Renal parenchymal damage- this can occur in [[obstructive uropathy]] or [[Acute kidney injury|AK]]I in which the renal parenchyma would not be able to effectively excrete potassium.<ref name="pmid2540370">{{cite journal| author=Clausen T, Everts ME| title=Regulation of the Na,K-pump in skeletal muscle. | journal=Kidney Int | year= 1989 | volume= 35 | issue= 1 | pages= 1-13 | pmid=2540370 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2540370  }} </ref>
*Renal parenchymal damage- this can occur in [[obstructive uropathy]] or [[Acute kidney injury|AK]]I in which the renal parenchyma would not be able to effectively excrete potassium.<ref name="pmid2540370">{{cite journal| author=Clausen T, Everts ME| title=Regulation of the Na,K-pump in skeletal muscle. | journal=Kidney Int | year= 1989 | volume= 35 | issue= 1 | pages= 1-13 | pmid=2540370 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2540370 }} </ref><ref name="pmid842984">{{cite journal| author=DeFronzo RA, Cooke CR, Goldberg M, Cox M, Myers AR, Agus ZS| title=Impaired renal tubular potassium secretion in systemic lupus erythematosus. | journal=Ann Intern Med | year= 1977 | volume= 86 | issue= 3 | pages= 268-71 | pmid=842984 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=842984  }} </ref><ref name="pmid12472794">{{cite journal| author=Sangkabutra T, Crankshaw DP, Schneider C, Fraser SF, Sostaric S, Mason K et al.| title=Impaired K+ regulation contributes to exercise limitation in end-stage renal failure. | journal=Kidney Int | year= 2003 | volume= 63 | issue= 1 | pages= 283-90 | pmid=12472794 | doi=10.1046/j.1523-1755.2003.00739.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12472794 }} </ref>
*[[Constipatiton]]-minor amount of potassium is also excreted by stools,so chronic constipation can lead to hyperkalemia however it is very rare.<ref name="pmid13242660">{{cite journal| author=SCRIBNER BH, FREMONT-SMITH K, BURNELL JM| title=The effect of acute respiratory acidosis on the internal equilibrium of potassium. | journal=J Clin Invest | year= 1955 | volume= 34 | issue= 8 | pages= 1276-85 | pmid=13242660 | doi=10.1172/JCI103174 | pmc=438696 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13242660  }} </ref>
*[[Constipation]]-minor amount of potassium is also excreted by stools,so chronic constipation can lead to hyperkalemia however it is very rare.<ref name="pmid13242660">{{cite journal| author=SCRIBNER BH, FREMONT-SMITH K, BURNELL JM| title=The effect of acute respiratory acidosis on the internal equilibrium of potassium. | journal=J Clin Invest | year= 1955 | volume= 34 | issue= 8 | pages= 1276-85 | pmid=13242660 | doi=10.1172/JCI103174 | pmc=438696 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13242660  }} </ref>


{| class="wikitable" style="cellpadding=0; cellspacing= 0; width: 900px;"
{| class="wikitable" style="cellpadding=0; cellspacing= 0; width: 900px;"
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* [[Hypothermia]]
* [[Hypothermia]]
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''''Renal parenchymal damage''''<br>
'''Renal parenchymal damage'''<br>
*[[Nephropathies]]
*[[Nephropathies]]
*[[Acute kidney injury]]
*[[Acute kidney injury]]
*[[Obstructive uropathy]]
*[[Obstructive uropathy]]<ref name="pmid7453754">{{cite journal| author=Batlle DC, Arruda JA, Kurtzman NA| title=Hyperkalemic distal renal tubular acidosis associated with obstructive uropathy. | journal=N Engl J Med | year= 1981 | volume= 304 | issue= 7 | pages= 373-80 | pmid=7453754 | doi=10.1056/NEJM198102123040701 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7453754  }} </ref>
*[[Amyloidosis]]
*[[Amyloidosis]]<ref name="pmid5789510">{{cite journal| author=Luke RG, Allison ME, Davidson JF, Duguid WP| title=Hyperkalemia and renal tubular acidosis due to renal amyloidosis. | journal=Ann Intern Med | year= 1969 | volume= 70 | issue= 6 | pages= 1211-7 | pmid=5789510 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5789510  }} </ref>
*[[Glomerulonephritis]]
*[[Glomerulonephritis]]
*[[Polycystic kidney disease]]
*[[Polycystic kidney disease]]
*[[Tubulointerstitial disease]]
*[[Tubulointerstitial disease]]
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'''''Defect in Potassium secretion'''''<br>
'''Defect in Potassium secretion'''<br>
''Primary hypoaldosteronism''
*'''Primary hypoaldosteronism'''<br>
* [[Addison's disease]]
** [[Addison's disease]]
*[[Autoimmune adrenalitis]]
**[[Autoimmune adrenalitis]]
*[[Congenital adrenal hyperplasia]]
**[[Congenital adrenal hyperplasia]]
*[[ACTH deficiency]]
**[[ACTH deficiency]]
''Secondary hypoaldosteronism''
*'''Secondary hypoaldosteronism'''<br>
*[[Renal tubular acidosis]]
**[[Renal tubular acidosis]]
*[[Hyporenimin hypoaldosteronism]]
**[[Hyporenimin hypoaldosteronism]]
*[[ACE inhibitors]]
**[[ACE inhibitors]]
''[[Pseudohypoaldosteronism]]''
*'''[[Pseudohypoaldosteronism]]'''
''[[Dehydration]]'',
*'''[[Dehydration]]''',
''[[Heart failure]]''
*'''[[Heart failure]]'''
| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
| style="font-size: 100; padding: 0 5px; background: #F5F5F5" align="left" |
*[[Constipation]]
*[[Constipation]]
Line 110: Line 120:


===Drugs causing hyperkalemia===
===Drugs causing hyperkalemia===
A lot of drugs are responsible for causing hyperkalemia. They do so by multiple mechanisms which are listed below:
A lot of drugs are responsible for causing hyperkalemia. They do so by multiple mechanisms which are listed below<ref name="pmid16394702">{{cite journal| author=Martyn JA, Richtsfeld M| title=Succinylcholine-induced hyperkalemia in acquired pathologic states: etiologic factors and molecular mechanisms. | journal=Anesthesiology | year= 2006 | volume= 104 | issue= 1 | pages= 158-69 | pmid=16394702 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16394702  }} </ref><ref name="pmid5394378">{{cite journal| author=Birch AA, Mitchell GD, Playford GA, Lang CA| title=Changes in serum potassium response to succinylcholine following trauma. | journal=JAMA | year= 1969 | volume= 210 | issue= 3 | pages= 490-3 | pmid=5394378 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5394378  }} </ref>:


{|
{|
Line 116: Line 126:
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mechanism causing hyperkalemia
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mechanism causing hyperkalemia
|-
|-
| style="background:#DCDCDC;" align="center" + |Amiloride
| style="background:#DCDCDC;" align="center" + |[[Amiloride]]
| style="background:#F5F5F5;" align="center" " + |Blocking sodium channels of luminal membrane of principal cells
| style="background:#F5F5F5;" align="center" " + |Blocking sodium channels of luminal membrane of principal cells
|-
|-
| style="background:#DCDCDC;" align="center" + |Spironolactone
| style="background:#DCDCDC;" align="center" + |[[Spironolactone]]
| style="background:#F5F5F5;" align="center" + |Mineralocorticoid receptor antagonist (competing with aldosterone)
| style="background:#F5F5F5;" align="center" + |Mineralocorticoid receptor antagonist (competing with aldosterone)
|-
|-
| style="background:#DCDCDC;" align="center" + |Beta Blockers
| style="background:#DCDCDC;" align="center" + |[[Beta Blockers]]
| style="background:#F5F5F5;" align="center" + |Decrease in cellular potassium uptake
| style="background:#F5F5F5;" align="center" + |Decrease in cellular potassium uptake
|-
|-
| style="background:#DCDCDC;" align="center" + |Calcium channel blockers
| style="background:#DCDCDC;" align="center" + |[[Calcium channel blockers]]
| style="background:#F5F5F5;" align="center" + |Inhibition of adrenal aldosterone biosynthesis
| style="background:#F5F5F5;" align="center" + |Inhibition of adrenal aldosterone biosynthesis
|-
|-
| style="background:#DCDCDC;" align="center" + |Succinylcholine
| style="background:#DCDCDC;" align="center" + |[[Succinylcholine]]
| style="background:#F5F5F5;" align="center" + |Leakage of potassium out of cells through depolarization of cell membranes
| style="background:#F5F5F5;" align="center" + |Leakage of potassium out of cells through depolarization of cell membranes
|-
|-
| style="background:#DCDCDC;" align="center" + |Mannitol
| style="background:#DCDCDC;" align="center" + |[[Mannitol]]
| style="background:#F5F5F5;" align="center" + |*Potassium shifts out of cells due to the body’s attempt to maintain isotonicity while undergoing a hypertonic infusion
| style="background:#F5F5F5;" align="center" + |*Potassium shifts out of cells due to the body’s attempt to maintain isotonicity while undergoing a hypertonic infusion
|-
|-
| style="background:#DCDCDC;" align="center" + |Heparin
| style="background:#DCDCDC;" align="center" + |[[Heparin]]
| style="background:#F5F5F5;" align="center" + |Inhibition of adrenal aldosterone biosynthesis
| style="background:#F5F5F5;" align="center" + |Inhibition of adrenal aldosterone biosynthesis
|-
|-
| style="background:#DCDCDC;" align="center" + |Digoxin
| style="background:#DCDCDC;" align="center" + |[[Digoxin]]
| style="background:#F5F5F5;" align="center" + |Inhibition of Na+/K+-ATPase
| style="background:#F5F5F5;" align="center" + |Inhibition of Na+/K+-ATPase
|-
|-
| style="background:#DCDCDC;" align="center" + |ACE inhibitors
| style="background:#DCDCDC;" align="center" + |[[ACE inhibitors]]
| style="background:#F5F5F5;" align="center" + |Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
| style="background:#F5F5F5;" align="center" + |Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
|-
|-
| style="background:#DCDCDC;" align="center" + |Angiotensin receptor-II antagonists
| style="background:#DCDCDC;" align="center" + |[[Angiotensin receptor-II antagonists]]
| style="background:#F5F5F5;" align="center" + |Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
| style="background:#F5F5F5;" align="center" + |Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
|-
|-
| style="background:#DCDCDC;" align="center" + |NSAIDs
| style="background:#DCDCDC;" align="center" + |[[NSAIDs]]
| style="background:#F5F5F5;" align="center" + |Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
| style="background:#F5F5F5;" align="center" + |Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
|-
|-
| style="background:#DCDCDC;" align="center" + |Cyclosporine,tacrolimus
| style="background:#DCDCDC;" align="center" + |[[Cyclosporine]],[[tacrolimus]]
| style="background:#F5F5F5;" align="center" + |Inhibition of adrenal aldosterone biosynthesis
| style="background:#F5F5F5;" align="center" + |Inhibition of adrenal aldosterone biosynthesis
|-
|-
| style="background:#DCDCDC;" align="center" + |Trimethoprine
| style="background:#DCDCDC;" align="center" + |[[Trimethoprim]]
| style="background:#F5F5F5;" align="center" + |Blocking of sodium channels in the luminal membrane of principal cells
| style="background:#F5F5F5;" align="center" + |Blocking of sodium channels in the luminal membrane of principal cells
|-
|-
Line 158: Line 168:


===Effects of hyperkalemia===
===Effects of hyperkalemia===
Potassium is vital for maintaining the membrane potential difference of cells. Increase in blood potassium levels lead to disruption in transmemebrane potential difference.<ref name="pmid2402122">{{cite journal| author=Conte G, Dal Canton A, Imperatore P, De Nicola L, Gigliotti G, Pisanti N et al.| title=Acute increase in plasma osmolality as a cause of hyperkalemia in patients with renal failure. | journal=Kidney Int | year= 1990 | volume= 38 | issue= 2 | pages= 301-7 | pmid=2402122 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2402122  }} </ref>
* Potassium is vital for maintaining the membrane potential difference of cells. Increase in blood potassium levels lead to disruption in transmemebrane potential difference.<ref name="pmid2402122">{{cite journal| author=Conte G, Dal Canton A, Imperatore P, De Nicola L, Gigliotti G, Pisanti N et al.| title=Acute increase in plasma osmolality as a cause of hyperkalemia in patients with renal failure. | journal=Kidney Int | year= 1990 | volume= 38 | issue= 2 | pages= 301-7 | pmid=2402122 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2402122  }} </ref>


*Hyperkalemia will [[depolarize]] the cells, thus the cells will remain excited initially.
*Hyperkalemia will depolarize the cells, thus the cells will remain excited initially.
*However, persistent depolarization will deactivate the sodium channels and sodium would not move inside the cells.
*However, persistent depolarization will deactivate the sodium channels and sodium would not move inside the cells.
*Inability of sodium to move inside the cells will cause them to become refractory to the stimulation.
*Inability of sodium to move inside the cells will cause them to become refractory to the stimulation.
*The cells would not respond to the electric signal and will remain in a depolarized state.
*The cells would not respond to the electric signal and will remain in a depolarized state.
Effect on heart-hyperkalemia can cause fatal cardiac arrhythmias in the form of [[ventricular fibrillation]] or even [[Sudden cardiac death|cardiac arrest]]. It effects the cardiac muscle by:
*Prolongation of membrane depolarization
*Slower myocardial conduction
*Shortening of the repolarization time
This will result in peaked [[T wave|T waves]], loss of [[P wave]], [[PR interval]] prolongation, [[Sine wave pattern|sine wave]] pattern and widening of [[QRS complex]].<ref name="pmid6101508">{{cite journal| author=Rosa RM, Silva P, Young JB, Landsberg L, Brown RS, Rowe JW et al.| title=Adrenergic modulation of extrarenal potassium disposal. | journal=N Engl J Med | year= 1980 | volume= 302 | issue= 8 | pages= 431-4 | pmid=6101508 | doi=10.1056/NEJM198002213020803 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6101508  }} </ref>


====== Effect on heart: ======
* Hyperkalemia can cause fatal cardiac arrhythmias in the form of [[ventricular fibrillation]] or even [[Sudden cardiac death|cardiac arrest]].
* It effects the cardiac muscle by:
**Prolongation of membrane [[depolarization]]
**Slower myocardial conduction
**Shortening of the [[repolarization]] time
*This will result in peaked [[T wave|T waves]], loss of [[P wave]], [[PR interval]] prolongation, [[Sine wave pattern|sine wave]] pattern and widening of [[QRS complex]].<ref name="pmid6101508">{{cite journal| author=Rosa RM, Silva P, Young JB, Landsberg L, Brown RS, Rowe JW et al.| title=Adrenergic modulation of extrarenal potassium disposal. | journal=N Engl J Med | year= 1980 | volume= 302 | issue= 8 | pages= 431-4 | pmid=6101508 | doi=10.1056/NEJM198002213020803 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6101508  }} </ref>


Nervous system and muscle are effected in the same manner resulting in muscle weakness and fatigue.
*Nervous system and muscle are effected in the same manner resulting in [[muscle weakness]] and [[fatigue]].
==Genetics==
==Genetics==
Genetic conditions associated with hyperkalemia include:<ref name="pmid21181208">{{cite journal| author=Lehnhardt A, Kemper MJ| title=Pathogenesis, diagnosis and management of hyperkalemia. | journal=Pediatr Nephrol | year= 2011 | volume= 26 | issue= 3 | pages= 377-84 | pmid=21181208 | doi=10.1007/s00467-010-1699-3 | pmc=3061004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21181208  }} </ref>
Genetic conditions associated with hyperkalemia include:<ref name="pmid21181208">{{cite journal| author=Lehnhardt A, Kemper MJ| title=Pathogenesis, diagnosis and management of hyperkalemia. | journal=Pediatr Nephrol | year= 2011 | volume= 26 | issue= 3 | pages= 377-84 | pmid=21181208 | doi=10.1007/s00467-010-1699-3 | pmc=3061004 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21181208  }} </ref>
Line 185: Line 197:


==Gross pathology==
==Gross pathology==
There is as such no gross changes in pathology in hyperkalemia. It usually depends on the underlying condition causing hyperkalemia.
* There is as such no gross changes in pathology in hyperkalemia. It usually depends on the underlying condition causing hyperkalemia.
 
==Microscopic pathology==
==Microscopic pathology==
There is as such no microscopic changes in pathology in hyperkalemia. It usually depends on the underlying condition causing hyperkalemia.
* There is as such no microscopic changes in pathology in hyperkalemia. It usually depends on the underlying condition causing hyperkalemia.
 


== References ==
== References ==


{{Reflist|2}}
{{Reflist|2}}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Jogeet Singh Sekhon

Overview

Potassium is the most abundant intracellular cation and is critically important for many physiologic processes. The normal range of potassium in blood is 3.5-5.1mEq/L. Hyperkalemia develops when the level of potassium exceeds 5.5 mEq/L in blood which can be due to an increase in intake of potassium, excessive production as seen in tissue breakdown, transcellular shift of potassium, ineffective elimination of potassium or due to some drugs. The potassium levels in the body are highly regulated mainly by renal excretion. The gut excretes a minimal amount of dietary potassium (approximately 10%). Hyperkalemia is very common in patients with chronic kidney disease as potassium is not effectively excreted from the body. Potassium is involved in maintaining transmembrane potential of the cells, so imbalance in potassium levels can lead to disruption of cell membrane potentials and can cause hyperexcitablity leading to fatal cardiac arrhythmias and may affect the nervous system.

Pathophysiology

Physiological role of potassium

Sodium-Potassium-ATPase Pump Source: Courtesy of Mariana Ruiz Villarreal, via Wikimedia commons[3]
Factors affecting transcellular shift of potassium

The distribution of potassium inside and outside the cells is maintained by various pumps, osmolarity, pH and the hormones including insulin, aldosterone, catecholamines and prostaglandins.

Role of kidneys

  • The potassium levels in the body are dependent on dietary intake, tissue breakdown, gastrointestinal absorption and losses and most important is renal regulation via absorption and secretion. Kidneys play an important role in keeping the balance of potassium.
  • At the glomerulus, potassium is freely filtered and then largely reabsorbed in the proximal tubule and thick ascending loop of Henle (>60 % of filtered potassium).
  • The cortical collecting duct receives 10–15% of filtered potassium and constitutes the kidney’s major site of potassium excretion.
  • Potassium excretion at the cortical collecting duct depends on the amount of sodium delivered there and the activity of aldosterone. It does so by the following ways.[5][6][7]
    • Increases intracellular K+ concentration by stimulating the activity of the Na+-K+-ATPase at the basolateral membrane.
    • Stimulates Na+ reabsorption across the luminal membrane, which increases the electronegativity of the lumen, thereby increasing the electrical gradient favoring K+ secretion. If the rate of delivery of sodium and water is very high in the distal tubules then it will cause more Na+ reabsorption and more K+ secretion.
  • Has a direct effect on the luminal membrane to increase K+ permeability.[8]
  • Alteration in the levels of potassium occur due to disruption in the above mentioned mechanisms that regulate potassium homeostasis.

Pathogenesis

  • Hyperkalemia means excessive potassium in the blood(>5.1 meq/L).
  • It can result from excessive potassium intake, increased tissue breakdown, increased transcellular shift or impaired excretion from the body [9].
Increased uptake
  • The only source of potassium to our body is by diet. If potassium rich diet is consumed or given parenterally, it can lead to hyperkalemia. However, in individuals with normal renal function, potassium levels are regulated and excess potassium is excreted
Transcellular shift
  • Change in extracellular pH-decrease in pH as in mineral acidosis leads to increased shift of potassium from intracellular to extracellular space.
  • Decrease in insulin as in diabetes mellitus, can lead to increased extracellular accumulation of potassium.
  • Increase in osmolarity as in hyperglycemia, will cause extracellular shift of potassium.
  • Decreased catecholamines or reduced function as with beta blockers use will lead to decreased uptake by cells resulting in extracellular accumulation of potassium.
Tissue breakdown

.

Impaired excretion
  • Potassium levels in body are regulated by the kidneys. Any impairment in the excretion mechanisms can result in hyperkalemia.
  • Reduced GFR(<15ml/min) results in decreased urine flow and hence decreased sodium and water delivery to the distal tubules resulting in decreased secretion of potassium.
  • Decrease in the levels of aldosterone as in primary hypoaldosteronism and secondary hypoaldosteronism results in impaired excretion of potassium.
  • Pseudohypoaldostrenism- the levels of aldosterone are within normal limits but there is resistance to aldosterone in the kidneys and is not able to exert its function.
  • Chronic kidney disease- the overall renal function is impaired resulting in decreased secretion of potassium as in various nephropathies.
  • Renal parenchymal damage- this can occur in obstructive uropathy or AKI in which the renal parenchyma would not be able to effectively excrete potassium.[12][13][14]
  • Constipation-minor amount of potassium is also excreted by stools,so chronic constipation can lead to hyperkalemia however it is very rare.[15]
Trans-cellular shifts Renal secretion impairment GI cause Increased tissue breakdown Increased intake of potassium

Renal parenchymal damage

Defect in Potassium secretion

  • Potasium rich diet-Spinach,green leafy vegetables,lettuce
  • Potassium supplements
  • Parenteral potassium citrate or potassium chloride

Drugs causing hyperkalemia

A lot of drugs are responsible for causing hyperkalemia. They do so by multiple mechanisms which are listed below[18][19]:

Drug Mechanism causing hyperkalemia
Amiloride Blocking sodium channels of luminal membrane of principal cells
Spironolactone Mineralocorticoid receptor antagonist (competing with aldosterone)
Beta Blockers Decrease in cellular potassium uptake
Calcium channel blockers Inhibition of adrenal aldosterone biosynthesis
Succinylcholine Leakage of potassium out of cells through depolarization of cell membranes
Mannitol *Potassium shifts out of cells due to the body’s attempt to maintain isotonicity while undergoing a hypertonic infusion
Heparin Inhibition of adrenal aldosterone biosynthesis
Digoxin Inhibition of Na+/K+-ATPase
ACE inhibitors Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
Angiotensin receptor-II antagonists Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
NSAIDs Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis and reduction in effective GFR
Cyclosporine,tacrolimus Inhibition of adrenal aldosterone biosynthesis
Trimethoprim Blocking of sodium channels in the luminal membrane of principal cells

Effects of hyperkalemia

  • Potassium is vital for maintaining the membrane potential difference of cells. Increase in blood potassium levels lead to disruption in transmemebrane potential difference.[20]
  • Hyperkalemia will depolarize the cells, thus the cells will remain excited initially.
  • However, persistent depolarization will deactivate the sodium channels and sodium would not move inside the cells.
  • Inability of sodium to move inside the cells will cause them to become refractory to the stimulation.
  • The cells would not respond to the electric signal and will remain in a depolarized state.
Effect on heart:

Genetics

Genetic conditions associated with hyperkalemia include:[22]

  • Hyperkalemic periodic paralysis
    • Hyperkalemic PP is an autosomal dominant condition with complete penetrance. The cause of hyperkalemic PP is a change in a gene that regulates the production of a protein (SCN4A) in the sodium channel of skeletal muscle. The gene is located in chromosome 17q23, and is known as SCN4A.
    • There is a defect in the sodium channels and sodium continues to leak out resulting in paralysis of the muscle.
    • During the episode of muscle paralysis,potassium leaks out into the bloodstream causing hyperkalemia.
  • Congenital adrenal hyperplasia
    • Congenital adrenal hyperplasia consists of several disorders resulting from defective enzymes and proteins involved in steroid and cortisol synthesis pathways. Defects in steroid biosynthesis are caused by several genetic mutations and may lead to delayed puberty, precocious puberty or ambiguous genitalia in specific disorders.
    • In 21 hydroxylase deficiency there is decreased production of aldosterone and hence hyperkalemia occurs.
    • In 3 beta hydroxysteroid dehydrogenase deficiency decreased production of aldosterone causes hyperkalemia.

Gross pathology

  • There is as such no gross changes in pathology in hyperkalemia. It usually depends on the underlying condition causing hyperkalemia.

Microscopic pathology

  • There is as such no microscopic changes in pathology in hyperkalemia. It usually depends on the underlying condition causing hyperkalemia.

References

  1. Giebisch G (1998). "Renal potassium transport: mechanisms and regulation". Am J Physiol. 274 (5 Pt 2): F817–33. PMID 9612319.
  2. De Nicola L, Bellizzi V, Minutolo R, Cioffi M, Giannattasio P, Terracciano V; et al. (2000). "Effect of dialysate sodium concentration on interdialytic increase of potassium". J Am Soc Nephrol. 11 (12): 2337–43. PMID 11095656.
  3. "File:Scheme sodium-potassium pump-it.svg - Wikimedia Commons".
  4. Lesko LJ, Offman E, Brew CT, Garza D, Benton W, Mayo MR; et al. (2017). "Evaluation of the Potential for Drug Interactions With Patiromer in Healthy Volunteers". J Cardiovasc Pharmacol Ther. 22 (5): 434–446. doi:10.1177/1074248417691135. PMC 5555446. PMID 28585859.
  5. Wang WH, Giebisch G (2009). "Regulation of potassium (K) handling in the renal collecting duct". Pflugers Arch. 458 (1): 157–68. doi:10.1007/s00424-008-0593-3. PMC 2730119. PMID 18839206.
  6. Giebisch GH, Wang WH (2010). "Potassium transport--an update". J Nephrol. 23 Suppl 16: S97–104. PMID 21170894.
  7. Frindt G, Shah A, Edvinsson J, Palmer LG (2009). "Dietary K regulates ROMK channels in connecting tubule and cortical collecting duct of rat kidney". Am J Physiol Renal Physiol. 296 (2): F347–54. doi:10.1152/ajprenal.90527.2008. PMC 2643862. PMID 19036846.
  8. Palmer LG, Antonian L, Frindt G (1994). "Regulation of apical K and Na channels and Na/K pumps in rat cortical collecting tubule by dietary K." J Gen Physiol. 104 (4): 693–710. PMC 2229228. PMID 7836937.
  9. Palmer LG, Frindt G (1999). "Regulation of apical K channels in rat cortical collecting tubule during changes in dietary K intake". Am J Physiol. 277 (5 Pt 2): F805–12. PMID 10564246.
  10. Thomson A, Kelly DT (1989). "Exercise stress-induced changes in systemic arterial potassium in angina pectoris". Am J Cardiol. 63 (20): 1435–40. PMID 2729129.
  11. Graber M, Subramani K, Corish D, Schwab A (1988). "Thrombocytosis elevates serum potassium". Am J Kidney Dis. 12 (2): 116–20. PMID 3400632.
  12. Clausen T, Everts ME (1989). "Regulation of the Na,K-pump in skeletal muscle". Kidney Int. 35 (1): 1–13. PMID 2540370.
  13. DeFronzo RA, Cooke CR, Goldberg M, Cox M, Myers AR, Agus ZS (1977). "Impaired renal tubular potassium secretion in systemic lupus erythematosus". Ann Intern Med. 86 (3): 268–71. PMID 842984.
  14. Sangkabutra T, Crankshaw DP, Schneider C, Fraser SF, Sostaric S, Mason K; et al. (2003). "Impaired K+ regulation contributes to exercise limitation in end-stage renal failure". Kidney Int. 63 (1): 283–90. doi:10.1046/j.1523-1755.2003.00739.x. PMID 12472794.
  15. SCRIBNER BH, FREMONT-SMITH K, BURNELL JM (1955). "The effect of acute respiratory acidosis on the internal equilibrium of potassium". J Clin Invest. 34 (8): 1276–85. doi:10.1172/JCI103174. PMC 438696. PMID 13242660.
  16. Batlle DC, Arruda JA, Kurtzman NA (1981). "Hyperkalemic distal renal tubular acidosis associated with obstructive uropathy". N Engl J Med. 304 (7): 373–80. doi:10.1056/NEJM198102123040701. PMID 7453754.
  17. Luke RG, Allison ME, Davidson JF, Duguid WP (1969). "Hyperkalemia and renal tubular acidosis due to renal amyloidosis". Ann Intern Med. 70 (6): 1211–7. PMID 5789510.
  18. Martyn JA, Richtsfeld M (2006). "Succinylcholine-induced hyperkalemia in acquired pathologic states: etiologic factors and molecular mechanisms". Anesthesiology. 104 (1): 158–69. PMID 16394702.
  19. Birch AA, Mitchell GD, Playford GA, Lang CA (1969). "Changes in serum potassium response to succinylcholine following trauma". JAMA. 210 (3): 490–3. PMID 5394378.
  20. Conte G, Dal Canton A, Imperatore P, De Nicola L, Gigliotti G, Pisanti N; et al. (1990). "Acute increase in plasma osmolality as a cause of hyperkalemia in patients with renal failure". Kidney Int. 38 (2): 301–7. PMID 2402122.
  21. Rosa RM, Silva P, Young JB, Landsberg L, Brown RS, Rowe JW; et al. (1980). "Adrenergic modulation of extrarenal potassium disposal". N Engl J Med. 302 (8): 431–4. doi:10.1056/NEJM198002213020803. PMID 6101508.
  22. Lehnhardt A, Kemper MJ (2011). "Pathogenesis, diagnosis and management of hyperkalemia". Pediatr Nephrol. 26 (3): 377–84. doi:10.1007/s00467-010-1699-3. PMC 3061004. PMID 21181208.