2015/6/301 Acid-Base Balance Ming-Jyh Sheu, PhD

2015/6/30 2 Purpose of acid-base balance & significance To maintain the pH of the body fluids within 7.35~7.45 The kidney maintains the pH of the body fluids within the normal range –[H + ] in body fluids 小於其它離子的百萬分之 一倍, its small size results in a high reactivity with binding sites on proteins –[H + ] plasma = 40 nEq/L or nM, pH = 7.4 –[Na + ] plasma = 140 mEq/L

2015/6/30 3 Regulation of [H + ] Chemical buffering by buffers in both ECF and ICF （快） Regulation of CO 2 concentration in the blood by alveolar ventilation in the lung （中） Control of [HCO 3 - ] ECF by the kidney （慢）

2015/6/30 4 CO 2 -HCO 3 - Buffering system CO 2 + H 2 O ↔ H 2 CO 3 ↔ HCO H + –K’ = [H + ] [HCO 3 - ] / [CO 2 ] [H 2 O] K’: depends on –Temperature （ at 37 O C, K’ = , pK’ = 6.1 ） –[CO 2 ] [H 2 O] 所代表的意思 代表 total amount of CO 2 dissolved in solution Most of this CO 2 is in gaseous form （ only 0.3% contained in H 2 CO 3 ） The amount of CO 2 is solution depends on its partial pressure （ pCO 2 ） and its solubility （ α ） CA

2015/6/30 5 Buffering CO 2 -HCO 3 - system: 在 ECF 中是一 個重要的緩衝系統 K’ = [H + ] [HCO 3 - ] / α pCO 2 –(37 O C 時： α= 0.03) [H + ] = k’ α pCO 2 / [HCO 3 - ] –- Log[H + ] = - log[K’] + - log α pCO 2 / - log[HCO 3 - ] –pH = pK’ + log [HCO 3 - ] / α pCO 2 –pH = log [HCO 3 - ] / 0.03pCO 2 （ Henderson-Hasselbalch equation ）

2015/6/30 6 [ H + ] = K （ pCO 2 / [HCO 3 - ] p ） This equation is useful in rapid interpretation of clinical acid-base balance disturbances [H + ] is directly related to pCO 2 [H + ] is inversely related to [HCO 3 - ] p 1.Metabolic acid-base disorder 代謝性酸減不平衡 : ECF [HCO 3 - ] 的改變 2.Respiratory acid-base disorder 呼吸性酸減不平衡 : a change in P CO 2 如果 pCO 2 or [HCO 3 - ] ↑, then the other must also ↑for [H + ] to remain constant 如果 pCO 2 or [HCO 3 - ] ↓, then the other must also ↓for [H + ] to remain constant Henderson -Hasselbalch equation

2015/6/30 7 Buffering CO 2 -HCO 3 - system CO 2 + H 2 O ↔ H 2 CO 3 ↔ HCO H + –CO 2 enters blood → ↑[H + ] –CO 2 leaves blood, and is exhaled from the lungs →  [H + ] Hypoventilation occurs, [H + ] p increases → respiratory acidosis Hyperventilation occurs, [H + ] p decreases → respiratory alkalosis

2015/6/30 8 Metabolic production of acid and alkali Nonvolatile acid –Cysteine, methionine → H 2 SO 4 –Lysine, arginine, and histidine → HCl –Catabolism of dietary lipids → phosphoric acid –Anaerobic metabolism → lactic acid –Aspartate and glutamate → HCO 3 -

2015/6/309 Renal regulation of H + balance

2015/6/30 10 Renal acid excretion To maintain acid-base balance –Kidney must excrete an amount of acid equal to the production of nonvolatile acid Replenish ( 補充 ) of HCO 3 -

2015/6/30 11 Net acid excretion (NAE) [(U NH4 +  V) + (U TA  V)] - (U HCO3 -  V) –U NH4 +  V: rate of excretion of NH 4 + –U TA  V: titrable acid –U HCO3 -  V: amount of HCO 3 - lost in the urine

2015/6/30 12 Reabsorption of HCO 3 - along the nephron

2015/6/30 13

2015/6/30 14 HCO 3 - 於集尿 管中再吸收 的機制 此處反應之 發生與代謝性 鹼中毒有關 ; Intercalated cells

2015/6/30 15 Factors regulating HCO 3 - reabsorption: 針對增加 H + secretion 部分探討 HCO 3 - (increased in filter load) Na + balance –Volume contraction →  Na + reabsorption,  HCO 3 - reabsorption ( 增加 H + secretion) [HCO 3 - ] p ↓ （ pH ↓ ） ---metabolic acidosis pCO 2 in plasma ↑ respiratory acidosis ↑Aldosterone secretion

2015/6/30 16 Aldosterone 1. 間接作用 a.Na + reabsorption 所 以 magnitude of lumen-negative voltage 增加 直接作用 a. 增加 H + 之 transporter

2015/6/30 17 Addition of new HCO 3 - to plasma 2 major buffers of H + in urine –Ammonia （ NH 3 ） –Dibasic phosphate （ HPO 4 -2 ）

2015/6/30 18 在此地方幾乎 已經無 HCO 3 - 之存在 此處 buffer 之產生應體內 酸鹼平衡之需要而有 buffer 之產生

2015/6/30 19

2015/6/30 20 Renal tubule acidosis （ RTA ） Urine acidification is impaired 無法分泌 H + 以平衡過多的代謝酸（ nonvolatile acid ），所以產生代謝性酸中毒 Defect in PT H + -secretion （ proximal RTA ） –Cystinosis 胱胺酸症 –Fanconi’s syndrome –Carbonic anhydrase inhibitors Defect in distal tubule H + -secretion （ distal RTA ） –Medullary sponge kidney –Amphotericin B –Secondary to urinary obstruction Treatment: ingest alkali (HCO 3 - )

2015/6/30 21 Response to acid-base disorders Respiratory defense –Metabolic acidosis: ↑H +  ↑ventilation rate Type-I-DM patient (keto acid 製造增 加 ): Kussmaul respiration: 呼吸肌會 疲勞, 所以呼吸代償會受損, 酸中毒 更嚴重 –Metabolic alkalosis:↓H +  ↓ventilation rate

2015/6/30 22 Response to acid-base disorders Renal defense –Secretion of H + –HCO 3 - reabsorbed –Production and excretion of NH 4 +

2015/6/30 23

2015/6/30 24

2015/6/30 25 DM patient: ketone bodies Diarrhea:

2015/6/30 26