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Acid-Base Balance. Ming-Jyh Sheu, PhD. 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
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Acid-Base Balance Ming-Jyh Sheu, PhD
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
Regulation of [H+] • Chemical buffering by buffers in both ECF and ICF(快) • Regulation of CO2 concentration in the blood by alveolar ventilation in the lung(中) • Control of [HCO3-]ECF by the kidney(慢)
CO2-HCO3- Buffering system CA • CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+ • K’ = [H+] [HCO3-] / [CO2] [H2O] • K’: depends on • Temperature(at 37 OC, K’ = 10-6.1, pK’ = 6.1) • [CO2] [H2O] 所代表的意思 • 代表 total amount of CO2 dissolved in solution • Most of this CO2 is in gaseous form(only 0.3% contained in H2CO3) • The amount of CO2 is solution depends on its partial pressure(pCO2)and its solubility(α)
Buffering CO2-HCO3- system: 在ECF中是一個重要的緩衝系統 • K’ = [H+] [HCO3-] / α pCO2 • (37 OC 時:α= 0.03) • [H+] = k’ α pCO2 / [HCO3-] • - Log[H+] = - log[K’] + - log α pCO2 / - log[HCO3-] • pH = pK’ + log [HCO3-] / α pCO2 • pH = 6.1 + log [HCO3-] / 0.03pCO2(Henderson-Hasselbalch equation)
Henderson-Hasselbalch equation • [ H+] = K(pCO2 / [HCO3-] p) • This equation is useful in rapid interpretation of clinical • acid-base balance disturbances • [H+] is directly related to pCO2 • [H+] is inversely related to [HCO3-]p • Metabolic acid-base disorder代謝性酸減不平衡: ECF [HCO3-]的改變 • Respiratory acid-base disorder呼吸性酸減不平衡: a change in PCO2 • 如果 pCO2 or [HCO3-] ↑, then the other must also ↑for [H+] to remain constant • 如果 pCO2 or [HCO3-] ↓, then the other must also ↓for [H+] to remain constant
Buffering CO2-HCO3- system • CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+ • CO2 enters blood → ↑[H+] • CO2 leaves blood, and is exhaled from the lungs → [H+] • Hypoventilation occurs, [H+] p increases → respiratory acidosis • Hyperventilation occurs, [H+] p decreases → respiratory alkalosis
Metabolic production of acid and alkali • Nonvolatile acid • Cysteine, methionine → H2SO4 • Lysine, arginine, and histidine → HCl • Catabolism of dietary lipids → phosphoric acid • Anaerobic metabolism → lactic acid • Aspartate and glutamate → HCO3-
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 HCO3-
Net acid excretion (NAE) • [(UNH4+V) + (UTA V)] - (UHCO3- V) • UNH4+V: rate of excretion of NH4+ • UTA V: titrable acid • UHCO3- V: amount of HCO3- lost in the urine
Intercalated cells HCO3-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;
Factors regulating HCO3- reabsorption: 針對增加H+ secretion部分探討 • HCO3- (increased in filter load) • Na+ balance • Volume contraction → Na+ reabsorption, HCO3- reabsorption (增加 H+ secretion) • [HCO3-]p ↓(pH ↓)---metabolic acidosis • pCO2 in plasma ↑---------respiratory acidosis • ↑Aldosterone secretion
Aldosterone • 間接作用 • Na+ reabsorption所以magnitude of • lumen-negative voltage增加 • 直接作用 • 增加H+之transporter Aldosterone
Addition of new HCO3- to plasma • 2 major buffers of H+ in urine • Ammonia(NH3) • Dibasic phosphate(HPO4-2)
此處buffer之產生應體內 酸鹼平衡之需要而有buffer 之產生 在此地方幾乎 已經無HCO3- 之存在
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 (HCO3-)
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
Response to acid-base disorders • Renal defense • Secretion of H+ • HCO3- reabsorbed • Production and excretion of NH4+
DM patient: ketone bodies Diarrhea: