REGULATION OF ACID-BASE & ELECTROLYTES Oleh: Dr. Husnil Kadri, M.Kes Bagian Biokimia Fakultas Kedokteran Universitas Andalas Padang

ASAM BASA.. [H+] pH

pH pH Acid Base Notasi pH diciptakan oleh seorang ahli kimia dari Denmark yaitu Soren Peter Sorensen pada thn 1909, yang berarti log negatif dari konsentrasi ion hidrogen. Dalam bahasa Jerman disebutWasserstoffionenexponent (eksponen ion hidrogen) dan diberi simbol pH yang berarti: ‘potenz’ (power) of Hydrogen.

Acid-Base Balance Normal pH of body fluids Arterial blood is 7.4 Venous blood and interstitial fluid is 7.35 Intracellular fluid is 7.0 Alkalosis or alkalemia – arterial blood pH rises above 7.45 Acidosis or acidemia – arterial pH drops below 7.35

Sources of Hydrogen Ions Most hydrogen ions originate from cellular metabolism Breakdown of phosphorus-containing proteins releases phosphoric acid into the ECF Anaerobic respiration of glucose produces lactic acid Fat metabolism yields organic acids and ketone bodies Transporting carbon dioxide as bicarbonate releases hydrogen ions

Hydrogen Ion Regulation Concentration of hydrogen ions is regulated sequentially by: Chemical buffer systems – act within seconds The respiratory center in the brain stem – acts within 1-3 minutes Renal mechanisms – require hours to days to effect pH changes

Acid/Base Homeostasis: Overview

Regulation of Blood pH The lungs and kidneys play important role in regulating blood pH. The lungs regulate pH through retention or elimination of CO2 by changing the rate and volume of ventilation. The kidneys regulate pH by excreting acid, primarily in the ammonium ion (NH4+), and by reclaiming HCO3- from the glomerular filtrate (and adding it back to the blood).

Carbonic acid/bicarbonate buffer system CO2 + H2O  H2CO3  H+ + HCO3- CA Carbonic acid is formed when CO2 combines with water. This reaction is catalysed by carbonic anhydrase Carbonic acid dissociates spontaneously to form a proton and a bicarbonate ion

The Lung Regulation Normal, unassisted breathing: Assisted breathing: An increase in arterial PCO2 acts through the respiratory centre to increase the rate of pulmonary ventilation A decrease in arterial PCO2 reduces the rate of ventilation Assisted breathing: A respirator is used to assist breathing by expelling CO2, thus reducing PCO2 in blood

The Lung Regulation When hypercapnia or rising plasma H+ occurs: Deeper and more rapid breathing expels more carbon dioxide Hydrogen ion concentration is reduced Alkalosis causes slower, more shallow breathing, causing H+ to increase

The Lung Regulation

The Renal Regulation Chemical buffers can tie up excess acids or bases, but they cannot eliminate them from the body The lungs can eliminate carbonic acid by eliminating carbon dioxide Only the kidneys can rid the body of metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent metabolic acidosis

The Renal Regulation The most important renal mechanisms for regulating acid-base balance are: Conserving (reabsorbing) or generating new bicarbonate ions Excreting bicarbonate ions Losing a bicarbonate ion is the same as gaining a hydrogen ion; reabsorbing a bicarbonate ion is the same as losing a hydrogen ion

Reabsorption of Bicarbonate

Hydrogen Ion Excretion

Hendersen-Hasselbalch (1909) CARA TRADISIONAL : Hendersen-Hasselbalch (1909)

BASA [HCO3-] GINJAL ASAM PARU Normal BASA [HCO3-] GINJAL pH = 6.1 + log Kompensasi  pCO2 CO2 Normal ASAM PARU CO2

Carbonic acid/bicarbonate buffer system pKa = 6.1 H2CO3  H+ + HCO3- ECF: Carbonic acid Bicarbonate ion The pKa of carbonic acid is 6.1 Carbonic acid is the major buffer in ECF The pH of blood can be determined using the Henderson-Hasselbalch equation

Henderson-Hasselbalch equation pH = pKa + log [HCO3-]/[H2CO3] pH = pKa + log [HCO3-]/0.03 x PCO2 7.4 = 6.1 + log 20 / 1 7.4 = 6.1 + 1.3 Plasma pH equals 7.4 when buffer ratio is 20/1 The solubility constant of CO2 is 0.03

pH atau [H+] DALAM PLASMA DITENTUKAN OLEH Cara Stewart ; pH atau [H+] DALAM PLASMA DITENTUKAN OLEH DUA VARIABEL VARIABEL INDEPENDEN VARIABEL DEPENDEN Stewart PA. Can J Physiol Pharmacol 61:1444-1461, 1983.

VARIABEL INDEPENDEN CO2 STRONG ION DIFFERENCE WEAK ACID pCO2 SID Atot

CO2 CO2 Didalam plasma berada dalam 4 bentuk sCO2 (terlarut) H2CO3 asam karbonat HCO3- ion bikarbonat CO32- ion karbonat Rx dominan dari CO2 adalah rx absorpsi OH- hasil disosiasi air dengan melepas H+. Semakin tinggi pCO2 semakin banyak H+ yang terbentuk. Ini yg menjadi dasar dari terminologi “respiratory acidosis,” yaitu pelepasan ion hidrogen akibat  pCO2

STRONG ION DIFFERENCE Definisi: Strong ion difference adalah ketidakseimbangan muatan dari ion-ion kuat. Lebih rinci lagi, SID adalah jumlah konsentrasi basa kation kuat dikurangi jumlah dari konsentrasi asam anion kuat. Untuk definisi ini semua konsentrasi ion-ion diekspresikan dalam ekuivalensi (mEq/L). Semua ion kuat akan terdisosiasi sempurna jika berada didalam larutan, misalnya ion natrium (Na+), atau klorida (Cl-). Karena selalu berdisosiasi ini maka ion-ion kuat tersebut tidak berpartisipasi dalam reaksi-reaksi kimia. Perannya dalam kimia asam basa hanya pada hubungan elektronetraliti.

STRONG ION DIFFERENCE SID KATION ANION Gamblegram Na+ 140 Mg++ Ca++ K+ 4 SID Na+ 140 Cl- 102 [Na+] + [K+] + [kation divalen] - [Cl-] - [asam organik kuat-] [Na+] + [K+] - [Cl-] = [SID] 140 mEq/L + 4 mEq/L - 102 mEq/L = 34 mEq/L KATION ANION

SKETSA HUBUNGAN ANTARA SID,H+ DAN OH- Konsentrasi [H+] Asidosis Alkalosis SID (–) (+) Dalam cairan biologis (plasma) dgn suhu 370C, SID hampir selalu positif, biasanya berkisar 30-40 mEq/Liter

WEAK ACID [Atot] (KA) = [A-].[H+] [Protein-] + [H+] [Protein H] disosiasi Kombinasi protein dan posfat disebut asam lemah total (total weak acid)  [Atot]. Reaksi disosiasinya adalah: [Atot] (KA) = [A-].[H+]

SID KATION ANION Gamblegram HCO3- 24 Na+ 140 Cl- 102 K+ 4 Weak acid Mg++ HCO3- 24 Ca++ K+ 4 SID Na+ 140 Weak acid (Alb-,P-) Cl- 102 KATION ANION

DEPENDENT VARIABLES H+ HCO3- OH- AH CO3- A-

INDEPENDENT VARIABLES Strong Ions Difference pH pCO2 Protein Concentration

Asidosis hiperkloremi APLIKASI H3O+ = H+ = 40 mEq/L Na 140 K HCO3 = 24 HCO3-  HCO3-  HCO3-  Mg SID Ca SID n SID  Alb P Alb Cl 115 Laktat/keto=UA P Alb Cl 102 Cl 102 P CL 95 Keto/laktat asidosis Asidosis hiperkloremi Alkalosis hipokloremi KATION ANION

KLASIFIKASI GANGGUAN KESEIMBANGAN ASAM BASA BERDASARKAN PRINSIP STEWART Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J Respir Crit Care Med 2000 Dec;162(6):2246-51

KLASIFIKASI ASIDOSIS ALKALOSIS I. Respiratori  PCO2  PCO2   ASIDOSIS ALKALOSIS I. Respiratori  PCO2  PCO2 II. Nonrespiratori (metabolik) 1. Gangguan pd SID a. Kelebihan / kekurangan air  [Na+],  SID  [Na+],  SID b. Ketidakseimbangan anion kuat: i. Kelebihan / kekurangan Cl-  [Cl-],  SID  [Cl-],  SID ii. Ada anion tak terukur  [UA-],  SID 2. Gangguan pd asam lemah i. Kadar albumin  [Alb]  [Alb] ii. Kadar posphate  [Pi]  [Pi] Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J Respir Crit Care Med 2000 Dec;162(6):2246-51

Fencl V, Am J Respir Crit Care Med 2000 Dec;162(6):2246-51 RESPIRASI M E T A B O L I K Abnormal pCO2 Abnormal SID Abnormal Weak acid Alb PO4- AIR  Anion kuat Cl- UA- Turun Alkalosis Turun kekurangan Hipo Asidosis Meningkat kelebihan Hiper Positif meningkat Fencl V, Am J Respir Crit Care Med 2000 Dec;162(6):2246-51

Anion Gap Described by Gamble in 1939 Electroneutrality Na+, Cl-, and HCO3 are measured ions Na + UC = Cl + HCO3 + UA UC = Sum of unmeasured cations UA = Sum of unmeasured anions The concept of an anion gap in blood was described in 1939 by Gamble. It was felt that the law of electroneutrality required that the number of positive charges contributed by serum cations should equal the number of negative charges contributed by serum anions. Sodium (Na), chloride (Cl), and bicarbonate (HCO3) are considered the measured ions. Potassium is ignored because its value changes so little. Thus, the concept of electroneutrality can be expressed by the simple equation: Na + UC = Cl + HCO3 + UA where UC (unmeasured cations) indicates the sum of the charges of the cations other than sodium and UA (unmeasured anions) equals the sum of the charges of all of the anions other than chloride and bicarbonate.

Anion Gap Unmeasured Cations: Unmeasured Anions: total 11 mEq/L Potassium 4 Calcium 5 Magnesium 2 Unmeasured Anions: total 23 mEq/L Sulfates 1 Phosphates 2 Albumin 16 Lactic acid 1 Org. acids 3 The “unmeasured cations” usually total about 11 mEq/L and include potassium (4 mEq/L), calcium (5 mEq/L), and magnesium (2 mEq/L). The “unmeasured” serum anions include sulfates (1 mEq/L), phosphates (2 mEq/L), proteins (16 mEq/L), lactic acid (1 mEq/L), and other organic acids (3 mEq/L). Ordinarily, the sodium concentration is about 140 mEq/L, and the sum of the CO2 content and chloride anions is about 128 mEq/L. Thus, the difference (or anion gap) between the sodium concentration and the sum of these two anions averages about 12 mEq/L. In patients with excessive acid production, the anion gap tends to be increased. On the other hand, in patients with metabolic acidosis due to loss of bicarbonate, the anion gap usually stays relatively normal.

Anion Gap = Na - (Cl + HCO3) Na + UC = Cl + HCO3 + UA 140 + 11 = 104 + 24 + 23 151 = 151 UA – UC = Na - (Cl + HCO3); Anion Gap = Na - (Cl + HCO3) The “unmeasured cations” usually total about 11 mEq/L and include potassium (4 mEq/L), calcium (5 mEq/L), and magnesium (2 mEq/L). The “unmeasured” serum anions include sulfates (1 mEq/L), phosphates (2 mEq/L), proteins (16 mEq/L), lactic acid (1 mEq/L), and other organic acids (3 mEq/L). Ordinarily, the sodium concentration is about 140 mEq/L, and the sum of the CO2 content and chloride anions is about 128 mEq/L. Thus, the difference (or anion gap) between the sodium concentration and the sum of these two anions averages about 12 mEq/L. In patients with excessive acid production, the anion gap tends to be increased. On the other hand, in patients with metabolic acidosis due to loss of bicarbonate, the anion gap usually stays relatively normal.

Change in Anion Gap vs HCO3 In simple AG Metabolic Acidosis decrease in plasma bicarbonate = increase in AG Anion Gap = 1 HCO3 Helpful in identifying mixed disorders In uncomplicated increased anion gap metabolic acidosis, the decrease (change) in plasma bicarbonate should be roughly equal to the increase (change) in the anion gap (that is, dAG/dHCO3 = 1.0). Whenever the anion gap changes much more or less than the bicarbonate, one should be suspicious of a coexisting or a mixed acid-base disorder. Ratios between 0.3 and 0.7 usually, but not always, indicate a mixed acid-base disorder or a preexisting low anion gap. Thus, the dAG/dHCO3 ratio is helpful in the diagnosis of mixed acid-base disorder because this ratio is usually close to 1.0 in typical organic acidoses. Values greater than 1.2 or less than 0.8 suggest the presence of a mixed acid-base disorder or an independent factor affecting the anion gap.

Sources Achmadi, A., George, YWH., Mustafa, I. Pendekatan “Stewart” Dalam Fisiologi Keseimbangan Asam Basa. 2007 Beaudoin, D. Electrolytes and ion sensitive electrodes. PPT. 2003. Ivkovic, A ., Dave, R. Renal review. PPT Kersten. Fluid and electrolytes. PPT. Marieb, EN. Fluid, electrolyte, and acid-base balance. PPT. Pearson Education, Inc. 2004 Rashid, FA. Respiratory mechanism in acid-base homeostasis. PPT. 2005. Silverthorn, DU. Integrative Physiology II: Fluid and Electrolyte Balance. Chapter 20, part B. Pearson Education, Inc. 2004 Smith, SW. Acid-Base Disorders. www.acid-base.com