Metabolic acidosis

1. 산-염기 불균형(Acid-Base Imbalance) Acid-base balance Metabolic acidosis Young Min Kim Handong University Sunlin Hospital Internal medicine

2. 대사성 산증은 체내의 pH가 7.35 이하로 낮아지는 경우를 뜻합니다. 수소 이온의 농도가 높아짐에 따라 중탄산 이온의 농도(normal serum HCO3-= 20~24)가 낮아지게 됩니다. 대사성 산증은 다음 세가지 원인에 의해 발생합니다. • (1)  강산성 물질이 체내에 첨가되어 버퍼가 되는 HCO3- 감소 • (2)  신장 또는 위장관을 통한 HCO3- 소실 • (3)  세포외액(ECF)의 급격한 희석(dilutional acidosis) • 대사성 산증은 또한 다음의 두 가지 범주로 나눌 수 있습니다. • a.    정상 음이온차(normal anion gap; hyperchloremic) • b.    높은 음이온차(increased anion gap)

3. The free [H+] is tiny and must be kept so for survival The normal extracellular H+ concentration is approximately 40 nanomol/L, roughly one-millionth the millimole per liter concetration of Na+, K+, Cl-, and HCO3-

4.  체내의 모든 기능은 산도(pH)가 7.4에서 최적으로 활성화 되며 이상 상태에 의한 급격한 산도 변화를 막기위한 버퍼 시스템과 폐, 신장 등의 조절 능력을 가지고 있습니다. • 기본적인 용어 • 산(Acid): 수소 이온(H+)을 제공하는 분자 • 염기(Base): 소소 이온(H+)을 받아들이는 분자 • 버퍼(Buffer): 약산, 약염기로 산도(pH)가 급격히 바뀌는 것을 막는데 도움을 줌 • Modified Henderson-Hasselbach equation: HCO3- 및 CO2에 의한 pH의 변화 • pH = PK’ + Log[(HCO3-)/(S.PCO2)] • 음이온차(Anion Gap)= UA – UC = (Na++ K+) – (Cl-+ HCO3-) •            정상 음이온차 = 약 16 mEq/L • PO2(partial oxygen concentration): 부분 산소 분압(mmHg) • PCO2(partial carbondioxide concentration): 부분 이산화탄소 분압(mmHg) • TCO2: 총 이산화 탄소 농도(mmEq/L) ≒ Bicarbonate(중탄산염 농도 mmEq/L)

5. A very large accumulation of H+ may kill Range of [H+] in plasma in clinical conditions • An enormous number of H+ are formed and consumed daily(70,000,000 nmol) in comparison with the amount of free H+ in the body at any one time(close to 4000 nmol) • Regulation of the H+ concentration at this low level is essential for normal cellular function because of the high reactivity of H+ ions, particularly with protein.

6. 정상적인 세포 외 H + 농도는 약 40 나노 몰 / L이며, Na +, K +, Cl-, 및 HCO3-의 리터당 리터당 백만 분의 일 밀리몰입니다. The normal extracellular H+ concentration is approximately 40 nanomol/L, roughly one-millionth the millimole per liter concetration of Na+, K+, Cl-, and HCO3-

7. Components of acid-base balance ① Fuels H+ 이산화탄소 : 폐 ③ CO2 ② HCO3- ④ H2o : 물 (소변) Kidney A H+ load is derived from oxidation of fuels Bicarbonate buffersultimately buffer this H+ load Change in alveolar ventilation to control the Pco2 The kidney regenerates HCO3-→ renal H+ excretion

8. A H+ load is derived from oxidation of fuelsBicarbonate buffersultimately buffer this H+ loadChange in alveolar ventilation to control the Pco2The kidney regenerates HCO3-→ renal H+ excretion • H + 부하는 연료의 산화에서 비롯됩니다 • 중탄산염 완충액은 궁극적으로이 H + 부하를 완충시킵니다 • Pco2를 제어하기 위해 폐포 환기의 변화 • 신장은 HCO3- → 신장 H + 배설을 재생합니다

9. The production and removal of H+ All of the following yield H+ All of the following remove H+ None of the following yields or removes H+

10. Rates of production and removal of H+ The total quantity of H+ that can be buffered per day is close to 1000mmol in a 70-kg person.

11. Overview of the net production of H+ Reactions that produce H+ • H+ are accumulating • H+ are not accumulating Much faster rate • L-lactic acid due to low supply of O2 • Exercise • Shock More slower rate • Ketoacidosis in DKA • L-lactic acid • Liver problem • PDH problem • Organic acids from gut • Anion from toxin • NH4+excretion problem • Anion are metabolized to neutral products almost as fast as they are formed • Ketoacid(Starvation) • L-lactic acid(usual rate) • Anions that are produced slowly and excreted with H+ and NH4+ • H2SO4 from proteins (Normal kidney)

12. Buffering of H+ Buffer curve describing the buffering of H+ 100 Number of H+added pK 50 0 [H+] • Buffer minimize the change in [H+] when an acid or alkali is added • Buffer are a very effective but temporary means of removing H+ from the body • The two most important buffer systems are the protein buffer system and the bicarbonate buffer system(BBS)

13. Two Buffer System-ICF, ECF Protein buffer system - ICF • The major non-bicarbonate buffer system(BBS) buffer is protein in the ICF • Recall that when H+ bind to protein, the charge shape, and possible function may change Bicarbonate buffer system(BBS) - ECF • The BBS is the initial buffer for a H+ load • The BBS is virtually the only buffer of the ECF, but it is also important in the ICF • A clinical evaluation of acid-base balance is made by examining the [H+], [HCO3-], and the Pco2 in plasma.

14. Teamwork in buffering ECF: + HCO3- + Lungs H+ H2O CO2 ICF: + HCO3- + H+ H2O CO2 Bº HB+ • A function of the BBS is to prevent H+ from binding to protein in the ICF • The BBS is used first to remove a H+ load, providing that hyperventilation occurs • The key to the operation of the BBS is the control of the Pco2

15. BBS: Importance of CO2 removal ① ② ③ When a patient had a H+ load that reduced the [HCO3-] in the ECF from 25 to 12.5 mmol/l. If the lungs were not present If the Pco2 had been maintained at 40 mmHg Normal state – ventilation removes CO2 and ventilation is stimulated by acidema

16. Renal generation of HCO3- Indirect reabsorption of filtered HCO3- • The first component of renal regulation of plasma [HCO3- ] – preventing the loss of the large quantity of filtered HCO3- • Amount: 4500meq/day c.f) total content of HCO3- in ECF: 375 meq Generation of new HCO3- -Titrable acidity • Filtered HPO42- -major urinary buffer • Amount: 10~40 mmol/day of H+ is buffered → same amount of new HCO3- is generated Generation of new HCO3- -NH4+ production and excretion • An important degree of flexibility to renal acid-base regulation • The rate of NH4+ production and excretion can be varied according to physiologic needs (extracellular pH dependent) • Amount: Normal value 30~40meq/day → severe metabolic acidosis 300meq/day

17. Renal generation of HCO3- Indirect reabsorption of filtered HCO3- Lumen Blood Blood HCO3- Na+ 3Na+ ATP H+ + HCO3- NHE H+ ATP AE1 H+ H+ 2K+ Cl- CA H2CO3 H2CO3 CA CA 3Na+ H2O + CO2 CO2 +H2O H2O + CO2 NBC HCO3- Proximal tubular cell Collecting tubular cell

18. Renal generation of HCO3- Generation of new HCO3- - Titrable acidity Lumen Blood Blood HPO42- Na+ 3Na+ ATP H+ + HCO3- NHE H+ ATP AE1 H+ H+ 2K+ Cl- CA H2CO3 CA 3Na+ H2O + CO2 CO2 +H2O NBC H2PO4- HCO3- Proximal tubular cell Collecting tubular cell

19. Renal generation of HCO3- Generation of new HCO3- - NH4+ excretion Lumen Blood Blood NH3 NH3 NH3 Na+ 3Na+ ATP H+ + HCO3- NHE H+ ATP AE1 NH4+ 2K+ Cl- CA Glutamine 3Na+ H2O + CO2 NBC α-keto glutarate NH4+ HCO3- Proximal tubular cell Collecting tubular cell

21. Initial diagnosis of acid-base disorders [H+] • High • Low • Normal H+ Mixed disorder if: • Pco2 and HCO3- both low • Pco2 and HCO3- both high • Plasma anion gap increased H+ acidemia • Alkalemia Pco2 High HCO3- Low Pco2 Low HCO3- High Metabolic acidosis Respiratory acidosis Metabolic acidosis Respiratory acidosis Examine all four parameters in plasma ([H+]-pH, [HCO3- ], Pco2, anion gap.

22. Treatment of metabolic acidosis Emergency measures Proper airway Adequate circulation O2 delivery Avoiding threats to life Determine the rate of H+ production The cause of the metabolic acidosis may pose independent threat to the patient (methanol overdose) Potassium depletion correction Treating the acidosis per se - bicarbonate therapy To assess the need for NaHCO3 therapy, use the plasma [HCO3-] instead of the pH Benefits vs. Risks Consider an abnormal [K+] in plasma Avoid a severe degree of hypokalemia when NaHCO3 is given to a patient with a severe degree of metabolic acidosis

23. Proper airway

25. 탄산수소나트륨주사액 8.4%

26. Development of metabolic acidosis + HCO3- + H+ H2O CO2 Added acids Loss of NaHCO3 No new A- (AG→) New A- (AG↑)

27. Overview of the etiology of metabolic acidosis • Overproduction of acids • Retension of anion in the plasma • L-Lactic acidosis(L-lactic acid) • Ketoacidosis(largely β-HB aicd) • Overproduction of organic acids in the GI tract(D-lactic acid) • Conversion of alcohols(methanol, ethylene glycol) to acids and poisonous aldehydes • Excretion of anions in the urine • Ketoacidosis and impaired renal reabsorption of β-HB • Inhalation of toluene(hippurate) • Actual bicarbonate loss(normal AG) • Direct loss of NaHCO3 • Gastrointestinal tract (e.g. diarrhea, ileus, fistula or T-tube drainage, villous adenoma, ileal conduit) • Urinary tract (e.g. proximal RTA, use of carbonic anhydrase inhibitors) • Indirect loss of NaHCO3 • Failure of renal generation of new bicarbonate (e.g. renal failure, hyperkalemia, medullary interstitial disease)

28. The anion gap in plasma Other cations Other anions A- HCO3- (25) Calculation for diagnostic convenience AG =[Na+]-[Cl-]-[HCO3-] Normal value: 12±2 meq/l Indicate the quantiry of added acid Is useful in following the patient’s response to therapy Cl- (103) Na+ (140)

29. Metabolic acidosis with increased anion gap Other cations Other cations Other anions Other anions A- A- L- Added anion HCO3- (25) HCO3- Cl- (103) Cl- Na+ (140) Na+ When an acid such as lactic acid is added, the [HCO3- ] will fall, and the HCO3- will be replaced with anion such as lactate anion (L-).

30. Metabolic acidosis with normal anion gap Other cations Other cations Other anions Other anions A- A- HCO3- HCO3- (25) Cl- (103) Cl- Na+ (140) Na+ With a loss of NaHCO3 , the [HCO3- ] will fall, but no new anion will be added, [Cl-] well be increased → hyperchloremic metabolic acidosis

31. Diagnostic approach metabolic acidosis Rise in AG=fall in HCO3- No rise in AG Rise in AG> fall in HCO3- Loss of NaHCO3 • GI tract, urine, indirect Metabolic alkalosis • Plasma ketone • Hypoxia • Decreased GFR Ketoacidosis L- lactic acidosis Renal failure Elevated Plasma osmolal gap • Methanol • Ethanol • Ethylene glycol Others • Type B L-lactic acidosis • D-lactic acidosis • Other acids

32. 임상 증상과 진단 •  임상증상 : 원발 질환과 관련되어 발생. 그러나 심한 산증의 경우 심근의 억압과 혈관 저항성이 감소되어 저혈압(hypotenstion), 폐수종(pulmonary edema), 심실 세동(ventricular fibrillation), 조직 저산소증(tissue hypoxia)을 유발할 수 있습니다.

33. 진단: 혈액 산-염기 분석 • 동맥혈 검사(ABGA)가정맥혈 검사보다는 pH, PCO2, PO2 수치에 대한 정확도가 높기 때문에 더 선호됩니다. pH, PCO2, tCO2에 대한 정맥혈 검사는 샘플이 적합한 방법으로 채취되었고 말초 순환에 장애가 발생하지 않은 경우에만 신뢰성을 가질 수 있습니다. 적합한 정맥혈 채혈은 주사기를 헤파린코딩한 주사기로 지혈대(tourniquet)를 이용하지 않은 상태로 말단부를 따뜻하게 한 후 채혈하여 즉시 검사하는 것입니다. •  실험실적 검사에서의 특징은 낮은 pH, 낮은 tCO2, 낮은 PCO2 입니다. 대사성산증시 혈장 칼륨 농도는 세포내로부터 칼륨의 유입으로 높을 수 있지만 각각 환축의 특정 질병 상황에 따라 정상 또는 저칼륨혈증도 또한 가능합니다.

34. 카리스마 (charisma)