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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
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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)
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CO2-HCO3- Buffering system
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 )
CA
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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( He
nderson-Hasselbalch equation)
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[ H+] = K ( pCO2 / [HCO3-] p )
This equation is useful in rapid interpretation of clinicalacid-base balance disturbances
[H+] is directly related to pCO2
[H+] is inversely related to [HCO3-]p
1. Metabolic acid-base disorder 代謝性酸減不平衡 : ECF [HCO3
-] 的改變2. 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 als
o ↑for [H+] to remain constant如果 pCO2 or [HCO3
-] ↓, then the other must also ↓for [H+] to remain constant
Henderson-Hasselbalch equation
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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
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Metabolic production of acid and alkali
Nonvolatile acid – Cysteine, methionine → H2SO4
– Lysine, arginine, and histidine → HCl– Catabolism of dietary lipids → phosphori
c acid– Anaerobic metabolism → lactic acid– Aspartate and glutamate → HCO3
-
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Renal acid excretion
To maintain acid-base balance– Kidney must excrete an amount of acid e
qual to the production of nonvolatile acid
Replenish ( 補充 ) of HCO3-
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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
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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
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Aldosterone
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 tran
sporter
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Addition of new HCO3- to plasma
2 major buffers of H+ in urine
– Ammonia( NH3)– Dibasic phosphate( HPO4
-2)
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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-)
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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
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Response to acid-base disorders
Renal defense
– Secretion of H+
– HCO3- reabsorbed
– Production and excretion of NH4+