2014-18 Acid production in the body Its in the production of approxmately 15,000 mmol of Co2 per day. Acidosis and Alkalosis ganic: lactate, metabolized by the liver and kidney the metabolism of proteins and other substances results in the generation A +H20一>RoH+08HP42-/0.2H2P4+18H The homeostatic response to acid load Chemical buffering Extracellular buffers 1. Chemical buffering by the extracellular and intracellular buffers 2. Changes in alveolar ventilation to control the 3. Alterations in renal H*excretion to regulate ne plasma HCO3- concentration. Henderson-Hasselbalch equation Henderson-Hasselbalch equation Eq.1)H++HCO3-<->H2C03<->H20+C02 Eq1)H++HCO3-<->H2C0O3<->H20+Co2 PCO2 PC02 X Eq2)[H+]=24 or by the henderson-Hasselbalch equation or by the Henderson-Hasselbalch equation (Eq. 3)pH 6.10+ log 03 PCO2 Acidosis: PCO2=1. X HCO3+8
2014-1-8 1 Acidosis and Alkalosis Hao Chuan-Ming Acid production in the body Carbonic acid: the metabolism of carbohydrates and fats (primarily derived from the diet) results in the production of approximately 15,000 mmol of CO2 per day. Non-carbonic acid: Organic: lactate, metabolized by the liver and kidney Inorganic: the metabolism of proteins and other substances results in the generation of noncarbonic acids (50 – 100 mEq, 1mEq/kg). Methionine —> glucose + urea + SO4(2-) + 2 H+ Arginine+ —> glucose (or CO2) + urea + H+ R-H2PO4 + H2O —> ROH + 0.8 HPO42- / 0.2 H2PO4- + 1.8 H+ The homeostatic response to acid load 1. Chemical buffering by the extracellular and intracellular buffers. 2. Changes in alveolar ventilation to control the PCO2. 3. Alterations in renal H+ excretion to regulate the plasma HCO3- concentration. Chemical buffering • Extracellular buffers • Intracelluar: bone Henderson-Hasselbalch equation (Eq. 1) H+ + HCO3- <—> H2CO3 <—> H2O + CO2 PCO2 (Eq. 2) [H+] = 24 x ———— [HCO3-] or by the Henderson-Hasselbalch equation [HCO3-] (Eq. 3) pH = 6.10 + log ——————— 0.03 PCO2 Henderson-Hasselbalch equation (Eq. 1) H+ + HCO3- <—> H2CO3 <—> H2O + CO2 PCO2 (Eq. 2) [H+] = 24 x ———— [HCO3-] or by the Henderson-Hasselbalch equation [HCO3-] (Eq. 3) pH = 6.10 + log ——————— 0.03 PCO2 Acidosis: PCO2=1.5 X HCO3 + 8
2014-18 Chemical buffering The homeostatic response to acid load Extracellular buffers Intracelluar buffer: bone Ca** release 1. Chemical buffering by the extracellular and intracellular buffers 2. Changes in alveolar ventilation to control the PCO2 3. Alterations in renal H* excretion to regulate the plasma HCO3- concentration The homeostatic response to acid load Acid production and excretion 1. Chemical buffering by the extracellular and intracellular buffers 2. Changes in alveolar ventilation to control the PCO2 3. Alterations in renal H* excretion to regulate e plasma HCo3- concentration add excretion and endogenous RENAL HYDROGEN EXCRETION Excretion of ht in a intercalated cells (1)reabsorption of the filtered HCO3 Tubular Lumen Collecting tubule P (2 )excretion of the 50 to 100 meg of H+ 2. Excretion of nh4+ in the urine oH+co→3Hco3
2014-1-8 2 Chemical buffering • Extracellular buffers • Intracelluar buffer: bone, Ca++ release, osteoclast activation The homeostatic response to acid load 1. Chemical buffering by the extracellular and intracellular buffers. 2. Changes in alveolar ventilation to control the PCO2. 3. Alterations in renal H+ excretion to regulate the plasma HCO3- concentration. The homeostatic response to acid load 1. Chemical buffering by the extracellular and intracellular buffers. 2. Changes in alveolar ventilation to control the PCO2. 3. Alterations in renal H+ excretion to regulate the plasma HCO3- concentration. RENAL HYDROGEN EXCRETION (1) reabsorption of the filtered HCO3- (2) excretion of the 50 to 100 meq of H+ produced per day 1. Formation of titratable acid 2. Excretion of NH4+ in the urine Tubular Lumen Collecting tubule Peritubular capillary H+ H2O2 OH- + CO2 3HCO3 - CA H+ ClATPase ATPase H+ K+ Excretion of H+ in a intercalated cells H+ H+
2014-18 Excretion of h+ in a intercalated cells Excretion of h* in a intercalated cells Collecting tubule Peritubular capillar Tubular Lumen Collecting tubule Peritubular cap HPO, H oH·CO→3Hco 叶HcO→3Hco3 Can be stimulated by low K Acid-base balance The kidneys must excrete the 50 to 100 meq of noncarbonic acid g The daily acid load is excreted as NH4'and H2(PO)- The daily acid load also cannot be excreted unless virtually all of the Regulation: The extracellular pH Can be independent o serum pH Steps in acid-base diagnosis Henderson-Hasselbalch equation (ABGs)and electrolytes simultaneously Eq1)H++HCO3-<->H2C0O3<->H20+Co2 PC02 Eq2)[H+]=24x or by the Henderson-Hasselbalch equation mare change in ( Ci] with change in( Nal Acidosis: PCO2=1. X HCO3+8
2014-1-8 3 Tubular Lumen Collecting tubule Peritubular capillary H+ H2O2 OH- + CO2 3HCO3 - CA HPO + H+ 4 2- H2PO4 ClATPase ATPase H+ K+ Excretion of H+ in a intercalated cells Tubular Lumen Collecting tubule Peritubular capillary H+ H2O2 OH- + CO2 3HCO3 - CA H+ + NH3 NH4 + ClH+ -ATPase NH3 Excretion of H+ in a intercalated cells Can be stimulated by low K Acid-base balance • The kidneys must excrete the 50 to 100 meq of noncarbonic acid generated each day. • The daily acid load is excreted as NH4+ and H2 (PO4 ). • The daily acid load also cannot be excreted unless virtually all of the filtered HCO3- has been reabsorbed, because HCO3- loss in the urine is equivalent to adding H+ ions to the body. • Regulation: – The extracellular pH – the effective circulating volume, – aldosterone, and – the plasma K+ concentration Can be independent of serum pH Steps in acid-base diagnosis • Obtain arterial blood gas (ABGs) and electrolytes simultaneously • Compare [HCO3-]on ABGs and electrolytes to verify accuracy • Calculate anion gap (AG) • Know 4 causes of high AG acidosis – Ketoacidsis – Lactic acid acidosis – Renal failure – Toxins • Know 2 causes of hyperchloremic or nongap acidosis – Bicarbonate loss from GI, – RTA • Estimate compensatory response • Compare ΔAG and ΔHCO3- • Compare change in [Cl] with change in [Na] Henderson-Hasselbalch equation (Eq. 1) H+ + HCO3- <—> H2CO3 <—> H2O + CO2 PCO2 (Eq. 2) [H+] = 24 x ———— [HCO3-] or by the Henderson-Hasselbalch equation [HCO3-] (Eq. 3) pH = 6.10 + log ——————— 0.03 PCO2 Acidosis: PCO2=1.5 X HCO3 + 8
2014-18 Metabolic acidosis Ketoacidosis Lactic acidosis Accumulation of endogenous acids(high anion gap) External losses of bicarbonate(normal anion gap hyperchloremic) Anion Gap Anion Gap ·AG=Na- Cl'-HCO3=12±2 will reduce ag charged. Presence of large amount orOsitive Renal failure Renal failure With mild to moderate reductions in gfR. the acidosis reflects decreased ammoniagenesis and is Despite a daily net positive acid balance it is unusual therefore hyperchloremic for [HCO3-to fall lower than 15 mmol/L. As kidney failure worsens, the calcium and a negative calcium balance ulfate phosphate, and other anions, produces an Chronic acidosis causes protein breakdown, muscle wasting, and a negative nitrogen balance. maintenance of the acid-base balance close to ormal can prevent these consequences
2014-1-8 4 Metabolic acidosis • Influx of organic acid into plasma (high anion gap) – Ketoacidosis – Lactic acidosis – Poisoning • Accumulation of endogenous acids (high anion gap) – Renal failure • External losses of bicarbonate (normal anion gap; hyperchloremic). – GI loss – Renal loss Anion Gap • AG=Na+ -Cl- -HCO3- = 12±2 • albumin: negative charged. Low serum albumin will reduce AG. • Paraprotein (Ig or light chains, MM): positive charged. Presence of large amount of paraprotein reduces AG. Anion Gap Renal failure • With mild to moderate reductions in GFR, the acidosis reflects decreased ammoniagenesis and is therefore hyperchloremic. • As kidney failure worsens, the kidney loses its ability to excrete various anions, and the accumulation of sulfate, phosphate, and other anions, produces an elevated AG. Renal failure • Despite a daily net positive acid balance, it is unusual for [HCO3−]to fall lower than 15 mmol/L. • The buffering of protons by bone results in loss of calcium and a negative calcium balance. • Chronic acidosis causes protein breakdown, muscle wasting, and a negative nitrogen balance. • Maintenance of the acid-base balance close to normal can prevent these consequences
2014-18 Treatment Hyperchloremic Metabolic Acidosis Alkali replacement Causes NaHCO3 Renal loss of alkali-Rta Gl loss of alkali Reciprocal changes in [Cl] and [HCO3 result in normal ag In the absence of such a relationship suggests a mixed disturbance Diarrhea afma NHa cronon Metabolic acidosis renal synthesis and excretion of NH4+, thus rinary pH is around Urinary NH4 levels are high: urine anion gap is Nopat Unne Anion Gap Proximal RTa(type 2) lower(normal: 26-28 mmol/). The distal nephron has a low capacity for Hco3 reabsorption. HCO3 18 mmol/, when all the filtered HCo3 is reabsorbed. espite systemic acidemia development, the urine ph is kaline. However under steady state, the urine can acidified to a ph of less than 5.5
2014-1-8 5 Treatment • Alkali replacement – NaHCO3 – Sodium citrate Hyperchloremic Metabolic Acidosis • Causes: – Renal loss of alkali – RTA – GI loss of alkali • Reciprocal changes in [Cl] and [HCO3] result in normal AG • In the absence of such a relationship suggests a mixed disturbance Diarrhea • Metabolic acidosis • Metabolic acidosis and hypokalemia increase renal synthesis and excretion of NH4+, thus urinary pH is around 6 • Urinary NH4 levels are high: urine anion gap is negative Proximal RTA (type 2) • The threshold for HCO3- reabsorption in the proximal tubule is lower (normal: 26 -28 mmol/l). • The distal nephron has a low capacity for HCO3 reabsorption. • Self-limited bicarbonaturia • In the steady state, the serum HCO3 concentration usually is 16 – 18 mmol/l, when all the filtered HCO3 is reabsorbed. • Despite systemic acidemia development, the urine pH is alkaline. However under steady state, the urine can be acidified to a pH of less than 5.5. HCO3 HCO3 HCO3