Hypokalemia hauv ntshav qab zib mellitus Setting

Ntsiab lus:ntshav qab zib mellitus;hypokalemia; mob raum thiab mob plawv

NEW HERBAL FORMULATION RAU DIABETIC KETOACIDOSIS

1. Taw qhia

Raws li Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Ntiaj Teb, ntshav qab zib mellitus (DM) pab txhawb rau 11.3% ntawm cov neeg tuag thoob ntiaj teb thiab kwv yees li 4.2 lab tus neeg tuag ntawm 20-79- cov neeg laus muaj hnub nyoog yog vim li cas tus mob ntawd [1 ]. DM-tus neeg tuag vim muaj qhov tsis sib xws hauv cheeb tsam, txij li 6.8% (qis tshaj) hauv Africa mus rau 16.2% (siab tshaj) hauv Middle East thiab North Africa. Kwv yees li ib nrab (46.2%) ntawm cov neeg tuag vim yog DM tshwm sim hauv cov neeg muaj hnub nyoog qis dua 60 xyoo. Africa muaj qhov siab tshaj plaws (73.1%) ntawm cov neeg tuag vim yog DM hauv cov neeg muaj hnub nyoog qis dua 60 xyoo, thaum Europe muaj qis tshaj (31.4%) [1]. Hypokalemia yog ib qho kev cuam tshuam ntawm electrolyte ntau tshaj plaws hauv kev kho mob thiab feem ntau yog theem nrab rau kev tswj tsis zoo glycemic cuam tshuam nrog polydipsia / polyuria, tshwj xeeb tshaj yog mob ntshav qab zib ketoacidosis (DKA) thiab hyperglycemic hyperosmolar xeev (HHS), plab hnyuv plab ua ke nrog hypomagnesemia, thiab diuretic siv rau kev tswj edema nyob rau hauv mob raum kab mob (CKD) los yog lub plawv tsis ua hauj lwm (HF) vim cardio-lub raum syndrome. Kev pheej hmoo siab dua ntawm atrial fibrillation, kev ua pa ntawm cov leeg ua pa, QT ntu ntu nce, torsade des pointes, thiab ventricular fibrillation, thiab, thaum kawg, kev mob siab dua thiab kev tuag hauv cov neeg mob ntshav qab zib mellitus nrog HF thiab CKD yog cov kev kho mob nrog hypokalemia [2]. Yog li ntawd, muaj kev sib koom ua ke ntawm cov ntshav qab zib hauv qib K + thiab kev tuag hauv cov neeg mob no (Daim duab 1). Tag nrho peb yam xwm txheej (CKD, HF, thiab DM) tuaj yeem cuam tshuam nrog cov neeg tuag ntau dua li ntawm 18- hli tom qab thaum piv nrog cov neeg tswj hwm. Tag nrho-ua rau kev tuag kuj tseem siab dua ntawm qhov siab, ob qho tib si hauv K + qhov tseem ceeb hauv qab 4.0 mEq / L thiab nyob rau hauv qhov tseem ceeb tshaj 6.0 mEq / L [2].

Daim duab 1. Kev tuag raws li cov ntshav cov poov tshuaj concentration hauv cov tib neeg uas muaj ntshav qab zib mellitus, cuam tshuam los yog tsis nrog lwm cov kab mob sib kis thiab kev faib tawm ntawm cov poov tshuaj concentration hauv cov pejxeem. (A) Mob ntshav qab zib mellitus tiv thaiv Pawg Tswj Xyuas. (B) Mob plawv tsis ua hauj lwm, Kab mob raum ntev, thiab ntshav qab zib mellitus tiv thaiv Pawg Tswj Xyuas. (C) Kev sib raug zoo ntawm cov ntshav cov poov tshuaj thiab kwv yees qhov tshwm sim ntawm kev tuag raws li txhua qhov kev sib xyaw thiab thaum muaj kev sib xyaw ua ke. CKD: Mob raum mob; DM: Mob ntshav qab zib mellitus; HF: Lub plawv tsis ua hauj lwm. Hloov los ntawm [2].

2. Hypokalemia thiab DM

2.1. Txhais, Prevalence, thiab tseem ceeb

Hypokalemia txhais tau tias yog plasmatic potassium (K +) concentration <3.5 mEq / L. Feem ntau ntawm hypokalemia hauv cov neeg muaj hnub nyoog 55 xyoos thiab nrog DM, nws txawv ntawm 1.0 thiab 1.2%. Qhov kev nthuav dav no ntau dua rau cov tib neeg uas muaj feem cuam tshuam nrog CKD thiab nce nrog hnub nyoog [3]. Ib qho ntawm cov kev pheej hmoo tseem ceeb cuam tshuam nrog hypokalemia yog kev siv cov tshuaj diuretics: 10 txog 50% ntawm cov neeg mob tau kho nrog cov tshuaj no tuaj yeem tsim hypokalemia [3,4]. Lwm cov tshuaj uas ua rau hypokalemia hauv cov neeg mob ntshav qab zib yog insulin, beta{13}} agonists (los ntawm kev ua kom cov sodium-potassium ATPase [Na+ -K+ -ATPase] twj tso kua mis), antiarrhythmic agents, glucocorticoids thiab mineralocorticoids, tshuaj tua kab mob (penicillin thiab aminoglycosides), tshuaj tua kab mob (amphotericin B), thiab kev siv tshuaj laxative ntau dhau. Kuj tseem muaj kev koom tes ntawm hypokalemia thiab kev pheej hmoo ntawm kev tsim ntshav qab zib hauv cov neeg mob ntshav qab zib [5]. Muaj pov thawj ntawm kev sib raug zoo ntawm cov ntshav qab zib K + thiab kev pheej hmoo ntawm kev tsim DM, tsis hais txog kev siv diuretic. Ib txoj kev tshawb nrhiav pom muaj kev phom sij ntawm 1.2–1.3 rau kev txhim kho ntawm qhov xwm txheej DM hauv cov neeg mob uas muaj cov poov tshuaj hauv qab no 5. Hypokalemia tshwm sim los ntawm kev siv thiazide diuretics kuj tseem cuam tshuam nrog kev pheej hmoo ntawm kev tsim DM. Txawm li cas los xij, kev tswj hwm thaum ntxov ntawm Thiazide-induced hypokalemia tuaj yeem kho cov piam thaj tsis kam tiv thaiv kev txhim kho ntshav qab zib hauv cov neeg no [7]. Txawm hais tias plasma insulin thiab ntshav qabzib nce ntxiv thiab cov ntshav qabzib K + txo qis hauv cov neeg mob ntshav siab nyob rau hauv hydrochlorothiazide monotherapy, tsis muaj kev hloov pauv ntawm cov piam thaj hauv cov ntshav tau pom tias qib K + ntau dua 4.0 mEq / L lossis qis dua 4.0 mEq / L [8].

Kev sib raug zoo ntawm hypokalemia thiab hyperglycemia yog raws li kev ua haujlwm ntawm ATP-sensitive potassium (KATP) channel hauv islet cells [9]. Yog li, thaum cov piam thaj nkag mus rau ß-cell los ntawm GLUT2 transporter nws yog metabolized rau qabzib -6-phosphate. Qhov nce hauv intracellular adenine nucleotides inhibits KATP thiab ua rau nws kaw. Tom qab daim nyias nyias depolarization activates voltage-dependent calcium (Ca2+) channels, uas ua rau insulin exocytosis tom qab nce Ca2+ intracellular. Yog li, hypokalemia yog txuam nrog kev loj hlob ntawm hyperglycemia los ntawm kev puas tsuaj ntawm potassium-dependent insulin tso tawm hauv kev teb rau cov piam thaj ntau dhau.

Hauv cov tib neeg noj qab haus huv, hypokalemia me me tuaj yeem ua rau tsis muaj tsos mob thiab ua rau me me lossis tsis muaj kev pheej hmoo dab tsi. Txawm li cas los xij, hauv cov tib neeg uas muaj DM, tshwj xeeb tshaj yog nyob rau hauv cov neeg uas muaj mob plawv, mob me mus rau nruab nrab hypokalemia yuav ua rau muaj kev pheej hmoo siab ntawm kev mob thiab kev tuag.

2.2. Cov Uas Tseem Ceeb ntawm Hypokalemia hauv Cov Neeg Nrog DM

Hauv cov tib neeg uas muaj DM, hypokalemia tshwm sim los ntawm peb pawg sib txawv ntawm cov xwm txheej: kev hloov pauv ntawm cov cellular (tshwj xeeb yog vim muaj cov tshuaj insulin ntau lossis los ntawm cov kab mob metabolic acidosis), kev poob qis (mob plab hnyuv, lub raum poob, lim ntshav, lossis hypomagnesemia), lossis tsis tsim nyog. kev [2–4,10]. Qhov laj thawj tseem ceeb ntawm hypokalemia hauv cov neeg uas muaj DM yog kev siv cov tshuaj insulin ntau, txawm tias thaum kho hom 1 DM (T1DM) thiab theem siab ntawm hom 2 (T2DM) lossis thaum sim kho cov xwm txheej hnyav xws li DKA thiab HHS. [11,12]. Lwm qhov kev pheej hmoo uas cuam tshuam nrog hypokalemia hauv cov neeg mob ntshav qab zib yog kev siv cov tshuaj diuretics, tshwj xeeb tshaj yog thiazides thiab voj diuretics. Hauv Table 1, peb sau cov ntsiab lus tseem ceeb ntawm hypokalemia raws li cov txheej txheem.

2.2.1. Transcellular Shifts Los ntawm Tshuaj

Insulin

Lub physiological teb rau insulin yog ua kom cov sodium-potassium ATPase (Na{1}}K+-ATPase) twj tso kua mis, txhawb kev nkag mus sai sai ntawm peripheral hlwb. Tsis tas li ntawd, cov tshuaj insulin-induced cov piam thaj rau hauv cov hlwb yog cov roj los tswj kev ua haujlwm ntawm Na+-K+-ATPase twj tso kua mis, muab kev tawm tswv yim rau K + kev thauj mus los no. Nyob rau theem ib txwm, insulin txhawb tsuas yog txo qis hauv cov ntshav K + concentration, uas yuav ua kom zoo los ntawm kev maj mam tso K + rov qab rau hauv cov ntshav. Txawm li cas los xij, cov koob tshuaj ntau ntawm cov tshuaj insulin, txawm tias vim yog kev tswj hwm tsis raug thaum kho T1DM thiab T2DM hauv cov theem siab lossis thaum kho cov teeb meem ntawm DM, tuaj yeem ua rau hypokalemia [13], uas yog feem ntau ua rau cov ntshav qis K +. concentration hauv cov neeg uas muaj DM [4].

Beta{0}} Agonists Sympathomimetic

Beta-2 cov neeg ua haujlwm yog lwm pab pawg tseem ceeb ntawm cov tshuaj uas txhawb nqa kev ua kom Na+ -K+ -ATPase twj tso kua mis. Cov piv txwv tseem ceeb ntawm Beta-2 agonists uas tuaj yeem ua rau hypokalemia yog cov tshuaj siv los kho mob hawb pob, xws li cov tshuaj tiv thaiv spasmodic thiab bronchodilators (albuterol, terbutaline, ephedrine, metaproterenol, isoproterenol, fenoterol, pirbuterol), decongestants (pseudo-cogestants). (ritodrine thiab nylidrin), dopamine, thiab HF kev kho mob (tshwj xeeb tshaj yog dobutamine). Hypokalemia tshwm sim los ntawm cov neeg ua haujlwm no tuaj yeem nyob ntev li ob peb teev thiab tuaj yeem ncav cuag qib qis li 2.5 mEq / L nyob ntawm qhov ntau npaum thiab txoj kev tswj hwm. Txawm hais tias theophylline tsis raug cais raws li ib qho -adrenergic agonist, nws yog ib qho tshuaj tiv thaiv spasmodic uas tseem txhawb nqa Na+ -K+ -ATPase kev ua. Cov tshuaj lom neeg ntawm tus neeg sawv cev no tuaj yeem ua rau muaj kev mob hypokalemia sai sai [4]. Lwm Cov Tshuaj Kho Mob ntawm cov tshuaj tiv thaiv kab mob, xws li verapamil, tsis muaj kev pheej hmoo ntxiv rau kev txhim kho hypokalemia hauv cov neeg mob ntshav qab zib. Txawm li cas los xij, kev haus luam yeeb nrog cov tshuaj verapamil siab tuaj yeem ua rau mob hnyav hypokalemia. Cov koob tshuaj ntau ntawm chloroquine thiab barium kuj tuaj yeem ua rau hypokalemia los ntawm inhibiting K + los ntawm cov hlwb [4].

2.2.2. Txo cov poov tshuaj tsis zoo los ntawm cov tshuaj diuretics

Ib qho ntawm feem ntau ua rau hypokalemia hauv cov neeg uas muaj DM yog kev siv cov tshuaj diuretics. Los ntawm txoj kev sib txawv, ob lub voj diuretics thiab thiazides nce Na + khoom rau cov kav dej. Qhov kev nce hauv Na + concentration hauv ntu no ua rau nws cov reabsorption, tsim cov electrochemical gradient uas nyiam tshem tawm cov poov tshuaj. Qib ntawm hypokalemia nyob ntawm ob qho tib si ntawm cov tshuaj diuretic siv thiab ntawm Na + concentration hauv cov ntu ntawm cov nephron. Ntxiv mus, kev sib xyaw ua ke ntawm ntau tshaj ib chav kawm ntawm cov tshuaj diuretics, xws li lub voj nrog thiazide lossis thiazide analog, potentiates K + secretion, uas tuaj yeem pab txhawb qhov pib ntawm hypokalemia. Drug-induced hypokalemia tuaj yeem cuam tshuam nrog ob qho tib si metabolic acidosis thiab alkalosis, los ntawm kev tuav cov bicarbonate (HCO3 −) los yog los ntawm inhibiting cov antiporters Na + thiab hydrogen (H +), induced, piv txwv li, los ntawm acetazolamide. Loop diuretics ua los ntawm inhibiting cov sodium-potassium-chloride (Na{10}}K+ -2 Cl−) co-transporter nyob rau hauv lub tuab ascending limb ntawm Henle lub voj [14]. Cov tshuaj no kuj inhibit qhov reabsorption ntawm magnesium (Mg2+) thiab Ca{15}}, los ntawm kev cuam tshuam qhov sib txawv ntawm cov tubular lumen thiab interstitium (lub ntsiab tsav tsheb rau reabsorption ntawm cov ions hauv ntu no. ). Kev nce hauv cov zis K + tawm tom qab lub voj diuretic siv yog vim muaj ntau yam txheej txheem: (1) Kev nce hauv Na + khoom, tshwj xeeb tshaj yog rau cov ducts sib sau ua ke, ua kom cov zis ntawm K + thiab H + (Na + reabsorption los ntawm cov hlwb tseem ceeb tsim cov electrochemical gradient uas. ua kom lub zais ntawm K + mus rau hauv tubular lumen, los ntawm ROMK [lub raum txheej medullary potassium] raws); (2) Ua kom cov renin-angiotensin-aldosterone system (RAAS) vim qhov ntim depletion thiab txo qis hauv sodium chloride (NaCl) thauj ntawm qhov ntom ntom ntom ntom; (3) Tso tawm vasopressin, teb rau Na + thiab ntim depletion. Kev nce hauv cov zis tso zis ntawm H + thiab K + tuaj yeem ua rau hypochloremic alkalosis xeev thiab hypokalemia, tshwj xeeb tshaj yog tias kev noj tsis txaus ntawm K + cuam tshuam. Thiazide diuretics inhibit Na+ -Cl- cotransporter (ENCC1 lossis TSC) nyob rau hauv lub apical daim nyias nyias ntawm cov hlwb hauv convoluted distal tubule [14]. Kev qhia ntawm cov protein no yog tswj hwm los ntawm aldosterone. Lub proximal tubule tej zaum yuav yog lub hom phiaj thib ob rau kev ua ntawm cov tshuaj no. Inhibitors ntawm Na+ -Cl- symport nce intratubular K + thiab H + los ntawm tib lub tswv yim zoo li lub voj diuretics. Nyob rau hauv cov ntaub ntawv ntawm cov diuretics (lub voj diuretics thiab thiazide diuretics), qhov ntau ntxiv ntawm intra-luminal Na + xa mus rau lub distal segments ntawm nephrons nkag mus rau lub hauv paus hlwb ntawm lub epithelial Na + channel (ENaC) channel. Qhov no tsim cov hluav taws xob tsis zoo hauv lub lumen. Ua kom Na+ - K+ -ATPase ua rau nws nqus Na+ rau hauv cov ntshav thiab pauv rau K+ . Kos los ntawm cov nqi hluav taws xob tsis zoo hauv lub lumen, K + yuav tawm ntawm lub xov tooj mus rau hauv lub lumen ntawm ROMK channel, ua rau hypokalemia. Nyob rau hauv lub intercalated cell ntawm cov ducts sau, lub stimulation ntawm lub H+ -K+ -ATPase twj tso kua mis, uas nrog rau cov tsis zoo nqi nyob rau hauv lub collecting ducts lumen, ua rau H + tawm intercalated hlwb mus rau hauv lub lumen. Yog li, alkalosis metabolic tshwm sim (cov ntshav HCO3 - concentration, 28-36 mmol / L) thiab ua rau hypokalemia zoo li [4]. Thiazide diuretics tuaj yeem txo cov ntshav qabzib siab thiab ua rau muaj kev cuam tshuam latent DM [15]. Lub mechanism ntawm impaired qabzib kam rau ua pom tau hais tias muaj kev hloov hauv cov piam thaj metabolism thiab impaired insulin secretion. Thiazide-induced DM, txawm li cas los xij, tsis tshwm sim kom muaj kev pheej hmoo ntawm cov hlab plawv ib yam li qhov xwm txheej DM [16].

Kev tswj hwm ntawm K + nrog thiazide diuretic tuaj yeem tiv thaiv cov xwm txheej hyperglycemic. Hauv cov neeg mob ntshav siab, Thiazide-induced hypokalemia tuaj yeem cuam tshuam kev kho mob. Thiazide diuretics tuaj yeem cuam tshuam cov lipid profile ntawm cov neeg mob ntshav qab zib, nce qib plasma ntawm tag nrho cov roj cholesterol, lipoprotein tsawg ntom ntom, thiab triglycerides [14]. Hauv cov neeg mob ntshav siab, chlorthalidone tau cuam tshuam nrog kev pheej hmoo ntawm hypokalemia (kev phom sij piv [HR], 2.7), CKD (HR, 1.24), mob raum tsis ua haujlwm (HR, 1.37), thiab DM [HR, 1.24] yam tsis muaj kev txo qis. hauv kev pheej hmoo ntawm cov kab mob plawv, thaum piv nrog hydrochlorothiazide [17].

Glucocorticoids thiab Mineralocorticoids

Glucocorticoids, xws li hydrocortisone, prednisone, thiab prednisolone tsis cuam tshuam ncaj qha rau K + excretion hauv ob lub raum. Qhov tseem ceeb, glucocorticoids feem ntau yog muab rau ntawm cov koob tshuaj uas tsim cov tshuaj mineralocorticoid tsawg heev (piv rau cortisol, prednisone, thiab prednisolone muaj 0.8 mineralocorticoid potency, whereas hydrocorti sone mineralocorticoid potency yog sib npaug rau cortisol, fludrocortisone muaj 125-15 potency corticoid). thaum piv rau cortisol, thiab dexamethasone tsis muaj mineralo-corticoid potency) kom tsis txhob muaj cov kev mob tshwm sim cuam tshuam nrog kev ua kom txoj hauv kev aldosterone, uas ua rau hypokalemia, ntim nthuav dav, thiab kub siab [18].

Mineralocorticoids, xws li fludrocortisone, tuaj yeem ua rau K + depletion nyob rau hauv lub distal nephron, los ntawm lawv qhov kev ua ntawm mineralocorticoid receptors, nyob rau hauv lub apical membrane ntawm tubular hlwb, uas txhawb kev qhia thiab kev ua ntawm Na+ -K+ - ATPase twj tso kua mis, ENaC, thiab ROMK raws, inducing Na + reabsorption thiab K + secretion [4]. Lwm yam tshuaj nrog glucocorticoid kev txiav txim, tshwj xeeb tshaj yog licorice derivatives (Glycyrrhiza glabra), xws li carbenoxolone los yog cottonseed derivatives (gossypol), kuj tuaj yeem ua rau hypokalemia vim lawv cov teebmeem inhibitory ntawm 11-hydroxysteroid dehydrogenase [19].

Tshuaj tua kab mob

Cov tshuaj tua kab mob beta-lactam, xws li penicillin, tuaj yeem ua rau lub raum K + poob, thaum siv tshuaj intravascularly thiab hauv cov koob tshuaj ntau, los ntawm kev nce Na + muab rau cov ntu ntu ntawm nephron. Aminoglycosides thiab amphotericin B tuaj yeem ua rau hypokalemia vim muaj kev cuam tshuam hauv electrolyte homeostasis. Kev kho mob nrog amphotericin B tuaj yeem ua rau hypokalemia thiab hypomagnesemia txog li 90% ntawm cov neeg mob, nyob ntawm qhov koob tshuaj. Ntau tshaj li ib lub tswv yim tau cuam tshuam nrog amphotericin B-induced electrolyte cuam tshuam xws li induction ntawm pore tsim nyob rau hauv daim nyias nyias ntawm lub raum tubular hlwb, hloov nyob rau hauv lub H+ -K+ -ATPase twj tso kua mis nyob rau hauv lub distal tubule. , ua rau lub raum tubular acidosis (RTA) hom I, thiab nce kev nqus ntawm Na + hauv plab hnyuv, nrog rau kev tso tawm ntawm K + hauv quav [20]. Aminoglycoside-induced hypokalemia tuaj yeem cuam tshuam nrog hypomagnesemia [21]. Vim lawv cov nqi zoo, aminoglycosides tuaj yeem khi rau polyva qiv cation receptors hauv cov tubule distal, inhibiting Mg2+ reabsorption. Lwm qhov kev pom zoo rau lub raum K + poob yog kev txhawb nqa ntawm sodium thiab chloride raws, ua rau hypokalemia metabolic alkalosis [21].

Oral Anti-Diabetics thiab Potassium

Hauv cov neeg rog rog nrog T2DM, linagliptin (ib hom 4 dipeptidyl-peptidase inhibitor) nce lub raum tso tawm ntawm Na + thiab K + thaum piv rau sulfonylurea glimepiride [22]. Kev siv cov tshuaj glycosuric (sodium-glucose cotransporter-2 inhibitors), tshwj xeeb tshaj yog empagliflozin thiab dapagliflozin, muaj ntau zuj zus rau cov neeg mob ntshav qab zib nrog CKD thiab HF. Cov tshuaj no txhawb kev txhim kho zoo heev hauv ntim los ntawm kev nce hauv cov zis tso zis thiab natriuresis, txawm hais tias lawv tsis tau pom muaj txiaj ntsig tseem ceeb ntawm K + kev puas tsuaj [23–25].