Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Viewers also liked
Viewers also liked (13)
Similar to Trastornos del potasio1
Similar to Trastornos del potasio1 (20)
Recently uploaded
Recently uploaded (20)
Trastornos del potasio1
- 2. Gerhard Giebisch Am J Physiol Renal Physiol 1998;274:F817-F833 ©1998 by American Physiological Society
- 3. Biff F. Palmer CJASN 2015;10:1050-1060©2015 by American Society of Nephrology
- 5. Biff F. Palmer CJASN 2015;10:1050-1060©2015 by American Society of Nephrology
- 6. ©2015 by American Society of Nephrology ©2014 by American Society of Nephrology Biff F. Palmer CJASN 2015;10:1050-1060
- 7. Arohan R. Subramanya, and David H. Ellison CJASN 2014;9:2147-2163 ©2014 by American Society of Nephrology
- 8. Biff F. Palmer CJASN 2015;10:1050-1060 ©2015 by American Society of Nephrology
- 9. Model of the “aldosterone paradox.” Two pathophysiological settings are depicted: hypovolemia (left) and hyperkalemia (right). Ewout J. Hoorn et al. JASN 2011;22:605-614 ©2011 by American Society of Nephrology
- 10. Creation of a more negative voltage in cells. J.H.M. Groeneveld et al. QJM 2005;98:305-316 The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
- 11. Approach to the patient with low K+ excretion. J.H.M. Groeneveld et al. QJM 2005;98:305-316 The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
- 12. Approach to the patient with high K+ excretion. J.H.M. Groeneveld et al. QJM 2005;98:305-316 The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
- 13. Plasma renin and aldosterone in the syndromes of mineralocorticoid excess. J.H.M. Groeneveld et al. QJM 2005;98:305-316 The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
- 14. Mechanism of TTP. (A) A traditional pathogenesis of TPP. An increased Na+–K+ ATPase activity directly induced by thyroid hormone and indirectly induced by hyperadrenergic activity, hyperinsulinemia, and androgen is mostly involved. Shih-Hua Lin, and Chou-Long Huang JASN 2012;23:985- 988©2012 by American Society of Nephrology Kir
- 15. trastornos asociados con mutaciones en el SCN4A. Lehmann-Horn F, Jurkat-Rott K, Rüdel R. Diagnostics and Therapy of Muscle Channelopathies – Guidelines of the Ulm Muscle Centre. Acta Myologica. 2008;27(3):98-113.
- 16. S. L. Venance et al. Brain 2006;129:8-17 © The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
- 17. Syed K. Haque et al. Nephrol. Dial. Transplant. 2012;27:4273-4287
- 18. Vieira H, Mendes L, Mendes P, da Silva JE. Classic Bartter syndrome: a rare cause o f failure to thrive in a child. BMJ Case Reports. 2012;2012:bcr0220125888. doi:10.1136/bcr.02.2012.5888. CASO CLINICO
- 19. Israel Zelikovic Nephrol. Dial. Transplant. 2003;18:1696-1700 European Renal Association–European Dialysis and Transplant Association Nephron Physiol 2006;104:p73–p80 (DOI:10.1159/000094001)
- 20. Kidney International (1998) 54, 1396–1410; doi:10.1046/j.1523-1755.1998.00124.x • Polihidramnios • Anormalidad bioquímica del líquido amniótico • Hipostenuria • Alcalosis metabólica con hipopotasemia • Nefrocalcinosis,hipercalciuria • Retardo del crecimiento • Potasio urinario alto • Niveles elevados de RA
- 21. Niño de 8 años de edad, desarrolló una convulsión generalizada que se prolongó durante 5 min y se produjo mientras jugaba . fue admitido en urgencias , estaba consciente y sin fiebre . Su altura del cuerpo era de 120 cm, el peso corporal 21,3 kg, la presión arterial 96/42 mmHg, frecuencia cardíaca 92 / min, y SpO 2 100%. Su historia pasada no tenía nada especial, excepto por quejarse de debilidad muscular después de jugar al fútbol. Su historia familiar reveló que su hermano mayor fue tratado con un anticonvulsivo causa de trastorno de hiperactividad y déficit de atención. Fue diagnosticado con convulsiones de causa desconocida,se le prescribio potasio L-aspartato (300 mg, dos tab / día) para la hipopotasemia y la carbamazepina (220 mg / día, dividida en dos tomas) asintomatico por un año . Sin embargo, un año después del ingreso en el hospital, presento alcalosis metabólica, hipopotasemia, hipomagnesemia. CASO CLINICO G. Graziani, C. Fedeli, L. Moroni, L. Cosmai, S. Badalamenti, C. Ponticelli 2010
- 22. Ewout J. Hoorn et al. JASN 2011;22:605-614 ©2011 by American Society of Nephrology Knoers NV, Levtchenko EN. Gitelman syndrome. Orphanet Journal of Rare Diseases. 2008;3:22. doi:10.118
- 23. BMC Biochem. 2008; 9 (Suppl 1): S5. Nephron Physiol 2006; 104: p73-p80 (DOI: 10.1159 / 000094001
- 24. Kidney International (2002) 62, 1-9; doi: 10.1046 / j.1523-1755.2002.00350.
- 26. A model of WNK-SPAK/OSR1 regulation of NCC and its role in the pathogenesis of Familial Hyperkalemic Hypertension (FHHt). Arohan R. Subramanya, and David H. Ellison CJASN 2014;9:2147-2163 ©2014 by American Society of Nephrology
Editor's Notes
- The cell model illustrates β2-adrenergic and insulin-mediated regulatory pathways for K+uptake. β2-Adrenergic and insulin both lead to K+ uptake by stimulating the activity of the Na+-K+-ATPase pump primarily in skeletal muscle, but they do so through different signaling pathways. β2-Adrenergic stimulation leads to increased pump activity through a cAMP- and protein kinase A (PKA)–dependent pathway. Insulin binding to its receptor leads to phosphorylation of the insulin receptor substrate protein (IRS-1), which, in turn, binds to phosphatidylinositide 3-kinase (PI3-K). The IRS-1–PI3-K interaction leads to activation of 3-phosphoinositide–dependent protein kinase-1 (PDK1). The stimulatory effect of insulin on glucose uptake and K+ uptake diverge at this point. An Akt-dependent pathway is responsible for membrane insertion of the glucose transporter GLUT4, whereas activation of atypical protein kinase C (aPKC) leads to membrane insertion of the Na+-K+-ATPase pump (reviewed in ref. 3).
- A cell model for K+transport in the proximal tubule. K+ reabsorption in the proximal tubule primarily occurs through the paracellular pathway. Active Na+ reabsorption drives net fluid reabsorption across the proximal tubule, which in turn, drives K+ reabsorption through a solvent drag mechanism. As fluid flows down the proximal tubule, the luminal voltage shifts from slightly negative to slightly positive. The shift in transepithelial voltage provides an additional driving force favoring K+ diffusion through the low-resistance paracellular pathway. Experimental studies suggest that there may be a small component of transcellular K+ transport; however, the significance of this pathway is not known. K+ uptake through the Na+-K+-ATPase pump can exit the basolateral membrane through a conductive pathway or coupled to Cl−. An apically located K+ channel functions to stabilize the cell negative potential, particularly in the setting of Na+-coupled cotransport of glucose and amino acids, which has a depolarizing effect on cell voltage.
- A cell model for K+transport in the distal convoluted tubule (DCT). In the early DCT, luminal Na+ uptake is mediated by the apically located thiazide-sensitive Na+-Cl− cotransporter. The transporter is energized by the basolateral Na+-K+-ATPase, which maintains intracellular Na+ concentration low, thus providing a favorable gradient for Na+ entry into the cell through secondary active transport. The cotransporter is abundantly expressed in the DCT1 but progressively declines along the DCT2. ROMK is expressed throughout the DCT and into the cortical collecting duct. Expression of the epithelial Na+ channel (ENaC), which mediates amiloride-sensitive Na+ absorption, begins in the DCT2 and is robustly expressed throughout the downstream connecting tubule and cortical collecting duct. The DCT2 is the beginning of the aldosterone-sensitive distal nephron (ASDN) as identified by the presence of both the mineralocorticoid receptor and the enzyme 11β-hydroxysteroid dehydrogenase II. This enzyme maintains the mineralocorticoid receptor free to only bind aldosterone by metabolizing cortisol to cortisone, the latter of which has no affinity for the receptor. Electrogenic-mediated K+ transport begins in the DCT2 with the combined presence of ROMK, ENaC, and aldosterone sensitivity. Electroneutral K+-Cl− cotransport is present in the DCT and collecting duct. Conditions that cause a low luminal Cl− concentration increase K+ secretion through this mechanism, which occurs with delivery of poorly reabsorbable anions, such as sulfate, phosphate, or bicarbonate.
- Role of magnesium in ROMK potassium channel function. Potassium is the most abundant intracellular cation, creating a large chemical gradient that favors the outward flow of K+ through ROMK. (Left panel) Normally, magnesium binds to a cytosol-exposed site in ROMK to limit this outward flow. (Right panel) During hypomagnesemia, fewer Mg2+ ions can bind to this site, and K+ is secreted more freely. Thus, magnesium deficiency causes K+ wasting. This likely explains why magnesium repletion is required to efficiently restore potassium concentrations to normal during concomitant hypomagnesemia and hypokalemia.
- Under normal circumstances, delivery of Na+to the distal nephron is inversely associated with serum aldosterone levels. For this reason, renal K+ excretion is kept independent of changes in extracellular fluid volume. Hypokalemia caused by renal K+ wasting can be explained by pathophysiologic changes that lead to coupling of increased distal Na+ delivery and aldosterone or aldosterone-like effects. When approaching the hypokalemia caused by renal K+ wasting, one must determine whether the primary disorder is an increase in mineralocorticoid activity or an increase in distal Na+ delivery. EABV, effective arterial blood volume.
- Model of the “aldosterone paradox.” Two pathophysiological settings are depicted: hypovolemia (left) and hyperkalemia (right). Aldosterone acts as a sodium retaining hormone during hypovolemia, leading to a low urinary Na+ excretion (left). Conversely, aldosterone acts as a K+-secreting hormone during hyperkalemia, leading to a high urinary K+ excretion (right). Hypovolemia stimulates angiotensin II (Ang II), which in turn increases aldosterone (Aldo). Both contribute to renal Na+ retention. Ang II stimulates Na+ transport in the proximal tubule by activating the NHE3. Ang II also increases the activity of the NCC in the early DCT1. Aldo activates both NCC and the ENaC in the late DCT (DCT2), CNT, and CD. Note that because Na+ transport is stimulated at three locations, the distal delivery of Na+ decreases, contributing to the low Na+ excretion. The effects of Ang II and Aldo are primarily mediated via a WNK–SPAK pathway, whereas the effects of Aldo on ENaC primarily involves SGK1. Unknown factors increase the WNK1–KS–WNK1 ratio, leading to inhibition of the ROMK, helping to conserve potassium during hypovolemia. In the setting of hyperkalemia, the opposite occurs, because direct effects of a high serum K+ level decrease the WNK1–KS-WNK1 ratio (right). This leads to an activation of ROMK, stimulating potassium secretion. The lower WNK1–KS-WNK1 ratio also increases WNK4, preventing Aldo from activating NCC (dashed line). However, Aldo is still capable of activating ENaC, which stimulates Na+ exchange for K+ in the collecting duct.
- Creation of a more negative voltage in cells. The circle depicts the cell membrane. The Na-K-ATPase pumps positive voltage out of cells, causing a large inside negative voltage (−60 to −90 mV). This ion pump is activated by β2-adrenergics. Insulin, by activating the Na+/H+ exchanger (NHE), causes the electroneutral entry of Na+ into cells, and thereby more positive voltage exit from cells via the Na-K-ATPase. K+ exits cells through ion channels that are in a sufficiently open configuration to approach, but not reach, the electrochemical equilibrium for K+.
- Approach to the patient with low K+ excretion.
- Approach to the patient with high K+ excretion.
- Plasma renin and aldosterone in the syndromes of mineralocorticoid excess. For details, see text. AME, apparent mineralocorticoid excess syndrome; BP, blood pressure; ENaC, epithelial Na channel.
- Mechanism of TTP. (A) A traditional pathogenesis of TPP. An increased Na+–K+ ATPase activity directly induced by thyroid hormone and indirectly induced by hyperadrenergic activity, hyperinsulinemia, and androgen is mostly involved. The open circle denotes the skeletal muscle cells and Na+/H+ exchanger (NHE). (B) Reduced K+ channel efflux in TPP. The enhanced Na+–K+ ATPase activity causes initial hypokalemia, and the reduced outward Kir current caused by hypokalemia, loss of function mutation, or hormone (adrenalin or insulin) -mediated inhibition on Kir channels can potentially inhibits total K+ efflux, leading to the trapping of K+ in the cell; a vicious cycle of hypokalemia-induced paradoxical depolarization and an inactivation of Na+ channel with muscle inexcitability and paralysis can result.
- Developmental features are critical in the assessment of patients with PP and the LQT syndrome to make the appropriate diagnosis and include: hypertelorism, small mandible, low set ears (A and B) and clinodactyly (C and D). Mankodi A, Tawil R. PP and related disorders. In: Gilman S, editor. MedLink Neurology. San Diego: MedLink Corporation. Available at www.medlink.com. Accessed February 9, 2005.
- Proximal tubule bicarbonate reabsorption. CAII/IV, carbonic anhydrase II/IV; NHE3, Na+/H+ exchanger 3; NBC1, Na+/HCO3− cotransporter.
- Transport pathways in the thick ascending limb of the loop of Henle (A) and the distal convoluted tubule (B). (A) Cl– reabsorption across the luminal membrane occurs via the Na+–K+–2Cl– co-transporter (NKCC2). This co-transporter is driven by the low intracellular Na+ and Cl– concentrations generated by the basolateral Na+–K+-ATPase and ClC-Kb, respectively. In addition, ROMK enables functioning of NKCC2 by recycling K+ back to the lumen. The lumen-positive electrical potential, which is generated by Cl– entry into the cell and K+ exit from the cell, drives paracellular Ca2+ and Mg2+ transport from lumen to blood. Activation of the basolateral calcium-sensing receptor (CaSR) inhibits the luminal ROMK channel which, in turn, results in decreased NaCl reabsorption and (secondary to the reduction in the intraluminal positive potential) increased urinary Ca2+ and Mg2+ excretion. (B) Cl– transport occurs via the luminal, thiazide-sensitive NaCl co-transporter (TSC). Cl– exit to blood is mediated by basolateral Cl– channels. Ca2+ and Mg2+ enter the cell via luminal voltage-activated Ca2+ and Mg2+ channels and exit the cell via basolateral Na+/Ca2+ and Na+/Mg2+ exchangers. The depicted apical Mg2+ channel and basolateral Na+/Mg2+ exchanger are putative. Variants of Bartter syndrome caused by defects in these transport mechanisms are depicted. BSND, Bartter syndrome with deafness; ADH, autosomal dominant hypocalcaemia.
- Model of NCC regulation by WNK kinases. NCC is trafficked as a monomer from the cytosol to the apical plasma membrane to become an inactive dimer (lower half of figure). Activation of the NCC dimer is achieved by phosphorylation through SPAK, stimulating NaCl transport (left). This process is regulated by WNK kinases. WNK4 (green symbol) inhibits the trafficking step of NCC by diverting it to the lysosome, a process that is mediated by sortilin and adaptin 3 (AP3). Conversely, WNK3 (red symbol) stimulates trafficking. WNK3 and WNK4 inhibit each other's activities. WNK4 is inhibited by WNK1 (red symbol), which in turn is inhibited by KS-WNK1 (blue and red symbol). WNK1 and WNK3 are also thought to influence the activity of SPAK, thereby controlling the phosphorylation and thus activation step of NCC. At present, it is unknown how the endocytic retrieval of NCC is regulated (question mark symbol). See text for details and abbreviations.
- A model of WNK-SPAK/OSR1 regulation of NCC and its role in the pathogenesis of Familial Hyperkalemic Hypertension (FHHt). (A) In the baseline inactive state, WNK4 suppresses NCC trafficking to the plasma membrane, holding the cotransporter in an intracellular storage pool. The kinase active form of WNK1 can reverse this process. The Kelch-like 3/Cullin-3 (KLHL3/CUL3) E3 ubiquitin ligase complex constitutively degrades the WNKs. (B) FHHt-associated mutations in WNK4 reduce binding to KLHL3, increasing WNK4 abundance and triggering NCC activation through the WNK effector kinases SPAK and OSR1. Additionally, FHHt-causing mutations in WNK4 reduce its inhibitory effect on NCC traffic (represented by the hatched bar-headed line), which releases NCC from its intracellular compartment, increasing its trafficking to the cell surface. Thus, FHHt mutations in WNK4 convert it into an NCC stimulator. (C) WNK1 gene mutations increase kinase-active WNK1 expression, which overcomes constitutive degradation by KLHL3/CUL3. Because kinase active WNK1 can inhibit wild-type WNK4 and activate SPAK/OSR1, increased WNK1 expression stimulates NCC surface delivery and phosphorylation. (D) Mutations in KLHL3 either reduce binding of KLHL3/CUL3 to WNK1 and WNK4 or disconnect CUL3 from KLHL3; in either case, the CUL3 E3 ligase is unable to mark WNK signaling complexes for degradation. Increased WNK1 and WNK4 abundance stimulates NCC trafficking to the surface and triggers NCC phosphorylation. FHHt-causing mutations in CUL3 also likely reduce its activity to WNKs, although the mechanism by which this occurs remains unknown. WNK, With-No-Lysine [amino acid=K] kinase.