Metabolic Alkalosis and Hypokalemia

Metabolic Alkalosis and Hypokalemia 내과 나기량 Definition of Metabolic Alkalosis  Metabolic alkalosis is a common primary acid-base disturbance manifested by an elevated arterial pH, increased bicarbonate, and increased PaCO2-  Often, but not always accompanied by hypochloremia and hypokalemia CNUH Renal Division Differential Diagnosis of an elevated serum HCO3- and Low Cl Metabolic alkalosis  Respiratory acidosis (Chronic) : renal compensation  ↑ HCO3 Therefore, diagnosis requires a concomitant arterial pH. CNUH Renal Division Respiratory compensation for MAK  PaCO2 will increase 6 mmHg for each 10 mEq/L increase in the [HCO3-]  PaCO2 will increase 0.75 mmHg per mEq/L increase in the [HCO3-]  PaCO2 = HCO3- + 15  When HCO3- in the range of 10-40 mEq/L CNUH Renal Division For Example!!  CHF on Diuretics medication(furosemide)  ABGA : 7.49 - ( ? /75) – 30 – 95%  Na / K / Cl ( 134 / 3.4 / 93 )  Δ HCO3- = 30-24 = 6  Q : Estimated PaCO2 ? A  HCO3- (30)+ 15 = 45 mmHg  ΔPaCO2 = Δ HCO3-(6)x 0.75 = 4.5 CNUH Renal Division Renal physiology : + and HCO K 3 Determinants of Plasma Potassium Concentration • Total content of K : 3500 mmol • ECF K content : 60-65 mmol (2%) • Internal Balance - transfer ECF↔ICF • External balnce - Renal K balance - Dietary K balnce Renal handling of potassium 65~70% Distal convoluted tubule Cortical collecting duct 100% 30% 10~15% Proximal convoluted tubule 25% 50% TAL 50% Outer medullary collecting duct FE K+ = [K+]u[Cr]s [K+]s[Cr]u 30% x100 K+ 140% Medullary collecting duct =10-20% or ~90mmol/day Fractional excretion of K+ Renal K+ transport in Proximal tubule Electrolyte transport in the thick ascending limb Lumen Ca2+, Mg 2+ Blood Na+/K+/2Clco-transporter Cl- channel Cl- Na+ K+ (CIC-kb) 2K + 3Na+ Na+/K+ ATPase 2 Cl- furosemide ATP sensitive K+ channel K+ K+ Cl- Apical membrane Basolateral membrane Collecting tubule principal cell: K+ secretion Lumen Epithelial Na+ Aldosterone Blood 3Na+ Channel Na+ ENaC K+ Amiloride + + + 2K + Na+/K+ ATPase Mineralocorticoid receptor H+ K+ ► K secretion factor 1. Luminal flow rate & distal Na delivery 2. Aldosterone 3. ECF K Apical membrane 4. Extracellular pH Basolateral membrane Collecting tubule intercalated cell : K+ reabsorpton Lumen 3Na+ 2K + Blood Na+/K+ ATPase K+ H+ Antiporter K+ K+ channel Apical membrane Basolateral membrane Pathophysiology : Phase of MAK  Generative Stage  Loss of acid ( vomiting, NG suction, diuretics )  Gain of HCO3- (renal or extrarenal sources)  Primary aldosteronism  Maintenance Stage (kidney loses ability to excrete bicarbonate efficiently)  Volume contraction, low GFR, Cl- or K+ depletion, high PCO2-, 2ndary hyperaldosteronism CNUH Renal Division Enteric Fluid Volume and Mineral Content Liter/da Na Saliva 1-2 10 60 150 100 K 30 9 10 5 100 Cl 10 90 90 100 15 HC03 30 0 70 20 60 Gastric Juice 2 Bile 2-3 Small Bowel 1 Colon Variable 40 (mEq/L) CNUH Renal Division HCO3- Retention by the Kidney  Cl- deficiency(ECF contraction), K+ deficiency, decrease in GFR and/or enhanced proximal bicarbonate absorption  2ndary hyperreninemic hyperaldosteronism Stimulates H+ secretion in CCT Repair with saline and K+ administration  Hypermineralocorticoidism and K+ deficiency induced by autonomous factors unresponsive to volume feedback Stimulation of H+ secretion in CCT >> effect of vol expansion to suppress proximal Na+/H+ Repair by surgical or phamacological means not by saline CNUH Renal Division Causes of Metabolic Alkalosis : Clinical situation  Vol. Contraction, hypokalemia  Vomiting, NG suction  Renal loss of H+, Cl-, and K+, diuretics, drug anions, magnesium deficiency  Vol. Expansion, hypertension, hypokalemia  High or Low renin (renal artery stenosis, adrenal adenoma)  Exogenous bicarbonate loads CNUH Renal Division ECF contraction, Normal BP, Hypokalemia and 2ndary hyperaldosteronism  Gastrointestinal origin  Vomiting and NG suction  Congenital chloridorrhea  Villous adenoma  Renal origin  Diuretics, edematous states  Mg+2 deficiency and hypoparathyroidism  Bartter and Gitelman syndrome  Non-reabsorbable anions (penicillin & carbeniciilin)  Recovery from lactic or ketoacidosis (overshoot) CNUH Renal Division Pathways and mediators of Na+ reabsorption NCCT Proximal tubule Distal tubule Gitelman syndrome Na+ 7% Na+ 60% Na+ 30% Na+ 2% Epithelial Na+ channel Na+/K+/2Cl- co-transporter Renal outer medullary K+ channel Cl- channel Loop of Henle Liddle’s syndrome PHA type I Bartter’s syndrome CNUH Renal Division Furosemide action in the thick ascending limb Lumen Ca2+, Mg 2+ Na+/K+/2Clco-transporter (furosemide sensitive) Cl- channel Blood ClNa+ (CIC-kb) 2K + 3Na+ Na+/K+ ATPase K+ 2 Cl- furosemide ATP sensitive K+ channel K+ K+ Cl- Apical membrane Basolateral membrane Lumen Na+ ClThiazide Blood Ca2+ Na+ 2K+ TSC ATP ATP ECaCl Ca++ 3Na+ Ca2+ Cl- Cell Thiazide at distal tubule ECF Expansion, Hypertension, Hypokalemia and mineralocorticoid excess  High Renin     Renal artery stenosis Renin-secreting tumor Estrogen therapy Accelerating hypertension  Low Renin  Primary aldosteronism  adenoma, carcinoma, hyperplasia  Adrenal enzyme defects  11β or 17α hydroxylase deficiency  Cushing syndrome  pituitary, adrenal adenoma, ectopic  Other’s  Licorice, carbenoxolone, chewer’s tobacoo, Liddle’s syndrome CNUH Renal Division Collecting tubule principal cell: K+ secretion Lumen Epithelial Na+ Aldosterone Blood 3Na+ Channel Na+ ENaC Amiloride + + + (amiloride sensitive) K+ 2K + Na+/K+ ATPase Mineralocorticoid receptor H+ K+ Apical membrane Basolateral membrane • Excessive Na reabsorption  HT, Vol exp, Renin↓ • Functional coupling of Na Reabsorption to K and H Secretion in distal nephron  MAK, HypoK 증 례 Case1  C.C : Hypokalemia로 consulted (NR)  P.I ( 69/M )  신경과에서 gait disturbance로 입원치료중 hypertension, hypokalemia, renal insufficiency로 consulted  HT은 3달전 진단, DM(-)  P/Ex : Abdominal bruit (Rt flank)  Lab     ABGA : 7.43-42/84-28-96% S-Na/K/Cl (137.6/2.1/93.8) , U-Na/K/Cl (44.8/24.9/60.0) BUN/Cr (24.8/1.95), 24hr UP=2.5 g, Ccr=31.2 ml/min CNUH Renal Division Case1  Kidney Sono 10.8 cm 7.2 cm Renin: 45.4 ng/ml/hr (0.15~2.33), Angiotensin 5193 pg/ml CNUH Renal Division Case1:Renal angiography CNUH Renal Division Case1-Ballooning CNUH Renal Division Case2  C.C : Facial edema w Wt gain. (6Mo PTA) (53 kg  62 kg)  P.I :  03’11월 부터 상기 Sx과 손,발의 저림, flushing 있어 선병원에서 검진함 : HBP, K 3.2 adal30mg, DCZ 25mg,ASA 100mg  항고혈압 약제 복용후 증상의 호전 없고 충혈, 안구 건조 및 입마름 증상 진행되어 내원  P/Ex  V/S : 110/80 – 70 -20 -36.7oC  Puffy face, anxious mood, Buffallo hump (?) CNUH Renal Division Case 2  LAB ABGA : 7.44-43/106-29-99 S-Na/K/Cl (144/2.7/101), U-Na/K/Cl (28/39/38) Hormone study Renin (0.83) (ng/ml/h:0.15-2.33) aldosterone (4.7) (ng/dl:1.0-16) serum cortisol 34.2-> 28.7 24hr urine cortisol : 837 CNUH Renal Division Case 2 - Brain MRI CNUH Renal Division CNUH Renal Division Case 3  C.C : Sudden Visual Acuity ↓ (3D PTA)  P.I 1년전 HBP Dx (No medication) 2개월 전부터 headache, nocturia발생  P/Ex V/S 220/90-96-20-36.7oC NVE (+) No PPh edema CNUH Renal Division Case3  LAB ABGA : 7.41-41/88-25.8-97% S-Na/K/Cl (130/2.5/96), U-Na/K/Cl (24/24/37) BUN/Cr (93/8.5) Ccr = 6.5 ml/min, 24h UP = 706 mg/d Hormone study Renin (2.7) (ng/ml/h:0.15-2.33) aldosterone (42.5) (ng/dl:1.0-16) Cortisol : WNL CNUH Renal Division Case3-Abd MRI CNUH Renal Division To make a long story short !!! Hypertension and Hypokalemia • Plasma renin activity (PRA) •Plasma aldosterone concentration (PAC) ↑PRA ↑PAC PAC-PRA≈10 Investigate for causes of 2nd hyperaldosteronism •RVHT •Diuretic use •Renin secreting tumor ↓PRA ↑PAC PAC-PRA≥10 And PAC ≥ 15ng/dL ↓PRA ↓PAC PAC-PRA≈10 Investigate for •Cong Adr Hyperplasia •Exoge mineralocorticoid •DOC-producing tumor Investigate for Primary aldosteronism •Cushing’s synd •11-β-OHSD deficiency •Altered aldo metabolism •Liddle’s syndrome •Malignant Phase HT •Coa of aorta When to consider Screening for Primary Aldosteronism • Hypertension and Hypokalemia • Resistant Hypertension • Adrenal Incidentaloma and HBP • Whenever considering 2nd HBP • Morning blood sampling in seated ambulant pt:  Plasma renin activity (PRA)  Plasma aldosterone concentration (PAC) PRA↓ PAC↑ PAC-PRA ratio ≥ 20 ng/dL per ng/mL per hr And PAC ≥ 15ng/dL(≥416 pmol/L) Investigate for Primary aldosteronism CNUH Renal Division 감사합니다!! Confirmed Primary aldosteronism CNUH Renal Division Treatment options for 1o Aldo CNUH Renal Division