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Acid-Base Balance Jianzhong Sheng MD, PhD Department of Pathophysiology School of Medicine Zhejiang University Objectives Explain how the pH of the blood is stabilized by bicarb buffer and define the terms acidosis and alkalosis. Explain how the acid-base balance of the blood is affected by CO2 and HCO3-, and describe the roles of the lungs and kidneys in maintaining acid-base balance. Explain how CO2 affects blood pH, and hypoventilation and hyperventilation affect acid-base balance. Explain how the interaction between plasma K+ and H+ concentrations affects the tubular secretion of these. Normal Acid-Base Balance Normal pH 7.35-7.45 Narrow normal range Compatible with life 6.8 - 8.0 pH 6.8 death 【H+】 160 7.35 7.45 acidosis alkalosis 40 7.8 death 16 nmol/L Structure of AQP1 Hg++ inhibitory site What are acidosis and alkalosis Normal pH: 7.40 (7.35-7.45) Acidosis: pH<7.35; Alkalosis: pH>7.45 Simple types of acidosis: Metabolic acidosis and Respiratory acidosis Simple types of alkalosis: Metabolic alkalosis and Respiratory alkalosis Mixed types of acid-base disorders pH pH of blood is 7.35 to 7.45 pH = 6.1 + log [HCO3-] 0.03 x Pco2 Types of Acids in the Body Volatile acids: Can leave solution and enter the atmosphere. H2CO3 (carbonic acid). Pco2 is most important factor in pH of body tissues. Types of Acids in the Body Fixed Acids: Acids that do not leave solution. Sulfuric and phosphoric acid. Catabolism of amino acids, nucleic acids, and phospholipids. Types of Acids in the Body Organic Acids: Byproducts of aerobic metabolism, during anaerobic metabolism and during starvation, diabetes. Lactic acid, ketones. Types of Acids in the Body Organic Acids: Byproducts of aerobic metabolism, during anaerobic metabolism and during starvation, diabetes. Lactic acid, ketones. Chemical Buffers Act within fraction of a second. Protein. HCO3-. Phosphate. Proteins COOH or NH2. Largest pool of buffers in the body. pk. close to pH in plasma. Albumin, globulins such as Hb. HCO3 pk. = 6.1. Present in large quantities. Open system. Respiratory and renal systems act on this buffer system. Most important ECF buffer. HCO3 Limitations Cannot protect ECF from respiratory problems. Cannot protect ECF from elevated or decreased CO2. Limited by availability of HCO3-. Phosphates pk. = 6.8. Low concentration in ECF, better buffer in ICF, kidneys, and bone. Respiratory System 2nd line of defense. Acts within min. -maximal in 12-24 hrs. H2CO3 produced converted to CO2, and excreted by the lungs. Alveolar ventilation also increases as pH decreases (rate and depth). Coarse , CANNOT eliminate fixed acid. Urinary Buffers Nephron cannot produce urine at pH < 4.5. IN order to excrete more H+, the acid must be buffered. H+ secreted into the urine tubule and combines with HPO42- or NH3. HPO42- + H+ H2PO4NH3 + H+ NH4+ Renal Acid-Base Regulation Kidneys help regulate blood pH by excreting H+ and reabsorbing HC03-. Most of the H+ secretion occurs across the walls of the PCT in exchange for Na+. Antiport mechanism. + and H+ in opposite directions. Moves Na Normal urine normally is slightly acidic because the kidneys reabsorb almost all HC03and excrete H+. Returns blood pH back to normal range. Reabsorption of HCO3 Apical membranes of tubule cells are impermeable to HCO3-. Reabsorption is indirect. When urine is acidic, HCO3- combines with H+ to form H2CO3-, which is catalyzed by ca located in the apical cell membrane of PCT (proximal convoluted tubule) . As [CO2] increases in the filtrate, CO2 diffuses into tubule cell and forms H2CO3. - and H+. H2CO3 dissociates to HCO3 HCO3- generated within tubule cell diffuses into peritubular capillary. Acidification of Urine Na+ + HCO3- H+ H+ H2CO3 H+ + HCO3- CA HPO42- NH3 H2O + CO2 NH4 + H2PO4- H2CO3 CA CO2 + H2O Urinary Buffers Nephron cannot produce urine at pH< 4.5. In order to excrete more H+, the acid must be buffered. H+ secreted into the urine tubule and combines with HPO42- or NH3. HPO42- + H+ H2PO4NH3 + H+ NH4+ Anion Gap The difference between [Na+] and the sum of [HC03-] and [Cl-]. [Na+] – ([HC03-] + [Cl-]) = 140 - (24 + 105) = 11 Normal = 12 ± 2 Clinicians use the anion gap to identify the cause of metabolic acidosis. Anion Gap Law of electroneutrality: Blood plasma contains an = number of + and – charges. The major cation is Na+. Minor cations are K+, Ca2+ , Mg2+. The major anions are HC03- and Cl-. (Routinely measured.) Minor anions include albumin, phosphate, sulfate (called unmeasured anions). Organic acid anions include lactate and acetoacetate,. Anion Gap In metabolic acidosis, the strong acid releases protons that are buffered primarily by [HC03-]. This causes plasma [HC03-] to decrease, shrinking the [HC03-] on the ionogram. Anions that remain from the strong acid, are added to the plasma. If lactic acid is added, the [lactate] rises. Increasing the total [unmeasured anions]. If HCl is added, the [Cl-] rises. Decreasing the [HC03 ]. Anion Gap in Metabolic Acidosis Salicylates raise the gap to 20. Renal failure raises gap to 25. Diabetic ketoacidosis raises the gap to 35-40. Lactic acidosis raises the gap to > 35 (>50). Largest gaps are caused by ketoacidosis and lactic acidosis. Simple Acid-Base Disturbance 1. Metabolic acidosis Concept: the primary disturbance is a decrease of [HCO-3] in the arterial plasma 1) Cause and pathogenesis lactic acidosis: hypoxia, diabetes liver disease ketoacidosis: diabetes, starvation ① Metabolic acidosis in severe renal failure: fixed acids increased AG salicylic acid acid poisoning: intake food GI: (loss of HCO-3) ② Metabolic acidosis in normal AG Kidney: (loss of HCO-3) diarrhea; intestinal suction intestinal fistula biliary fistula early renal failure: NH3 secretion H+ secretion Renal tubular acidosis: H+ secretion depressant of C.A. acetazolamide intake of ClNaCl, NH4Cl Hyperkalemia 2) Compensatory regulation ① Buffer: ② Respiratory compensation ③ Cellular compensation ④ Renal compensation [H+] : C.A. H+ secretion NH3 secretion [HCO-3] / [H2CO3] = 20:1 compensation acidosis [HCO-3] / [H2CO3] < 20:1 decompensation acidosis (SB AB BB BE PaCO2 AB < SB) Discussion of case 1 Method: 1. pH 2. primary factor and parameter 3. secondary factor and compensation 4. expected range of compensation №1: patient, female, 46, chronic pyelitis pH 7.32 (Normal: 7.35-7.45) PaCO2 28mmHg (Normal: 35-45mmHg) SB 13.6mmol/L (Normal: 22-27mmol/L) BE -15.3mmol/L (Normal: -3.0-+3.0mmol/L) 3) Effect on body ① Cardiovascular system hyperkalemia arrhythmia [H+] contractility peripheral resistance ② Central nervous system [H+] ATP , γ-amino butyric acid (somnolence, coma) 4) Principles of treatment ① Correction of underlying disorders; ② Administration of NaHCO3; ③ Correction of water-electrolyte disturbances. Summary of Metabolic Acidosis Gain of fixed acid or loss of HCO3-. Plasma HCO3 decreases. PCO2 decreases. pH decreases. 2. Respiratory acidosis Concept: The primary disturbance is an elevation in plasma [H2CO3] 1) Cause and pathogenesis Barbital depression of CNS head injury ①CO2 breathe paralysis of respiratory muscles out disease of airway or lung chest injury ② Inhalation of CO2 2) Compensation Buffer: Hb-/HHb Cells: exchange of H+ and K+ Kidney: secretion of H+ and NH3 (PaCO2 SB AB BB BE AB>SB) 3) Effect on body ① CNS CO2 celebral vascular dilation, intracranial pressure headache、fatigue CO2 narcosis respiration ② Cardiovascular system 4) Principles of treatment improve ventilation. Do not add NaHCO3 №2: Patient, male, 45, chronic bronchitis pH 7.26 (Normal: 7.35-7.45) PaCO2 60mmHg (Normal: 35-45mmHg) BB 46.2mmol/L (Normal: 45-55mmol/L) SB 22mmol/L (Normal: 22-27mmol/L) BE -7.5mmol/L (Normal: -3.0-+3.0mmol/L) after treatment pH 7.34 PaCO2 70mmHg BB 58mmol/L BE 5.5mmol/L Respiratory Acidosis PCO2 increases. Plasma HCO3 increases. pH decreases. 3. Metabolic alkalosis Concept: the primary disturbance is an increase of [HCO-3] in the arterial plasma 1) Causes and pathogenesis ① loss of H+ digestive tract vomiting; gastric suction(loss of HCl) diuretics distal flow rate (furosemide) blood volume Ald hyperaldosteronism H+-Na+exchange kidney H+-K+exchange between hypokalemia intra- and extra-cell renal secretion of H+ hypochloremia renal secretion of H+ ②intake of base NaHCO3 transfusion of banked blood (citrate) Gastric fluid loss and AB balance Esophagus Blood vessel Stomach Cl - H+ HCO3- H+ HCO3- H2CO3 Pancreas - HCO3- HCO3- Na+ Duodenum Cl Cl H2CO3 H+ Na+ H+ Na+ 2) Compensation of the body ① respiration compensation are limited (hypoxia) ② cells compensation hypokalemia ③ kidney pH inhibition of carbonic anhydrase (C.A.) secretion of H+ (SB AB BB BE PaCO2 AB>SB) 3) Effects on body inhibition of glutamate decarboxylase ① CNS γ-amino butyric acid dysphoria insanity pH brain-vessel dizziness contraction brain delirium O2 dissociation hypoxia Coma curve shifting to left ② neuromuscle pH free Ca2+ ③ hypokalemia arrhythmia tic 4) Principles of treatment loss of H+ digestive tract diuretic ; hypokalemia 0.9%NaCl; KCl hyperaldosteronism antisterone; diamox(乙酰唑胺) Metabolic Alkalosis Loss of fixed acid or gain of HCO3-. Plasma HCO3 increases. PCO2 increases. pH increases. 4. Respiratory alkalosis Concept: the primary disturbance is decrease of [H2CO3] in plasma 1) cause and pathogenesis hypotonic hypoxia pneumonia hyperventilation hysteria, fever, [NH3] hyperthyroidism misoperation of ventilator respiration (slight inhibition) 2) Compensation cells (exchange of H+-K+) kidney secretion of H+ (PaCO2 ; SB AB BB BE ; AB<SB) 3) Effects on body It is as same as metabolic alkalosis. dizziness and convulsion are happened easily 4) Principles of treatment inhalation of 5%CO2 Mixed acid-base disturbance 1. Dual acid-base disturbance 1) metabolic acidosis plus respiratory acidosis heart beat [HCO-3] stop character pH respiration PaCO2 2) metabolic alkalosis plus respiratory alkalosis hepatic NH3 PaCO2 character [HCO- ] pH failure diuretic 3 3) respiratory acidosis plus metabolic alkalosis pulmonary heart disease diuretic pH ± 4) respiratory alkalosis plus metabolic acidosis infective shock fever pH ± 5) metabolic acidosis plus metabolic alkalosis ketoacidosis(diabetes) vomiting pH ± 2. triple acid-base disturbance 1) respiratory acidosis; metabolic acidosis and alkalosis pulmonary heart disease; vomiting 2) respiratory alkalosis; metabolic acidosis and metabolic alkalosis fever; vomiting; diarrhea (food poisoning) №3. Patient, male, 47, purulent appendicitis. He was treated with abdominal suction and persistent gastrointestinal decompression after operation. pH PaCO2 SB BE K+ Cl- 7.56 (Normal: 35-45mmHg) 50mmHg (Normal: 35-45mmol/L) 34mmol/L (Normal: 22-27mmol/L) 10mmol/L (Normal: -3.0-+3.0mmol/L) 3.2mmol/L (Normal: 3.5-5.5mmol/L) 105mmol/L (Normal: 103mmol/L) Respiratory Alkalosis PCO2 decreases. Plasma HCO3 decreases. pH increases. The scope of compensatory responses of acid-base disorders Acute respiratory acidosis: △[HCO-3]=0.1×△PaCO2 ±1.5 Chronic respiratory acidosis: △[HCO-3]=0.4×△PaCO2 ±3.0 Acute respiratory alkalosis: △[HCO-3]=0.2×△PaCO2 ±2.5 Chronic respiratory alkalosis: △[HCO-3]=0.5×△PaCO2 ±2.5 Metabolic acidosis: △PaCO2 =1.2×△[HCO-3] ±2.0 Metabolic alkalosis: △PaCO2 =0.7×△[HCO-3] ±5.0 Summary of Simple ABD 1. 概念: 根据原发变化因素及方向命名 2. 代偿变化规律: 代偿变化与原发变化方向一致 代偿变化规律 代酸 [HCO-3] [H2CO3]↓ 代碱 [HCO-3] [H2CO3]↑ 呼酸 [HCO-3]↑ [H2CO3] 呼碱 [HCO-3]↓ [H2CO3] 3. 基本特征: 呼吸性ABD,血液pH与其它指标变化方 向相反 代谢性ABD,血液pH与其它指标变化方 向相同 4. 原因和机制 代酸: 固定酸生成↑及HCO3-丢失↑→HCO3-降低 呼酸: CO2排出减少吸入过多,使血浆[H2CO3]升高 代碱: H+丢失, HCO3-过量负荷,血HCO3-增多 呼碱: 通气过度CO2呼出过多,使血中[H2CO3]降低 对机体的影响 CNS 离子改变 酸中毒 抑制性紊乱 血钾增高 其它 血管麻痹 心律失常 收缩力降低 碱中毒 兴奋性紊乱 血钾降低 肌肉痉挛 或麻痹 6. 代偿调节 1. 代谢性ABD:各调节机制都起作用,尤 其是肺和肾 2. 呼吸性ABD:肺一般不起作用; 急性紊乱细胞内外二对离子交换; 慢性紊乱肾调节 酸碱平衡紊乱类型的判断 一划五看简易判断法 一划:将多种指标简化成三 项,并用箭头表示其升降 SB AB BB↓,BE(-)↑ pH [HCO3-] [H2CO3] [H+] PaCO2↓ 五看: 一看pH定酸碱 1 pH升高:失偿型碱中毒 pH降低:失偿型酸中毒 2 pH正常可能是 (1) 酸碱平衡 (2) 代偿性单纯性ABD (3)混合性相消型ABD 二看原发因素定代呼 1.病史中有"获酸","失碱"或 相反情况,为代谢性ABD 2.病史中有肺过度通气或相反情况, 为呼吸性 ABD 例1 病史? [HCO-3]↓ [H2CO3]↓ pH N 三看“继发性变化”定单混 1 "继发性变化"的方向 (1) 与原发性变化方向一致: 单纯型ABD or 混合型ABD (2)与原发性变化方向相反: 混合型 例2 PaCO2↑,HCO-3↓, pH ↓↓↓ 例3 PaCO2↑ HCO-3↑ pH 接近正常 2.“继发性变化”的数值 (代偿预计值) (1)数值在代偿预计值范围内,为单 纯型ABD (2)数值明显超过或低于代偿预计值, 为混合型ABD 四看AG定单混,定两三 1.AG升高>14mmol/L,提示有代酸, > 30 mmol/L肯定有代酸 2 在AG增高型代酸,AG增高数=[HCO3-] 降低数.即ΔAG=Δ[HCO3-] 潜在[HCO3-]=[HCO3-]实测值+ΔAG 例7 一位肺心病合并腹泻病人, pH = 7.12, PaCO2 = 84.6 mmHg, HCO-3 = 26.6mmol/L, Na+= 137 mmol/L,Cl-=85 mmol/L。该病 人发生何种酸碱平衡紊乱? AG = Na+- (HCO-3 + Cl- )= 137-(26.6+85) = 25.4 mmol/L 五看临床表现做参考 Discussion of cases Method: 1. pH 2. primary factor and parameter 3. secondary factor and compensation 4. expected range of compensation №1: patient, female, 46, chronic pyelitis pH 7.32 (Normal: 7.35-7.45) PaCO2 28mmHg (Normal: 35-45mmHg) SB 13.6mmol/L (Normal: 22-27mmol/L) BE -15.3mmol/L (Normal: -3.0-+3.0mmol/L) №2: Patient, male, 45, chronic bronchitis pH 7.26 (Normal: 7.35-7.45) PaCO2 60mmHg (Normal: 35-45mmHg) BB 46.2mmol/L (Normal: 45-55mmol/L) SB 22mmol/L (Normal: 22-27mmol/L) BE -7.5mmol/L (Normal: -3.0-+3.0mmol/L) after treatment pH 7.34 PaCO2 70mmHg BB 58mmol/L BE 5.5mmol/L №3. Patient, male, 47, purulent appendicitis. He was treated with abdominal suction and persistent gastrointestinal decompression after operation. pH PaCO2 SB BE K+ Cl- 7.56 (Normal: 35-45mmHg) 50mmHg (Normal: 35-45mmol/L) 34mmol/L (Normal: 22-27mmol/L) 10mmol/L (Normal: -3.0-+3.0mmol/L) 3.2mmol/L (Normal: 3.5-5.5mmol/L) 105mmol/L (Normal: 103mmol/L) №4. 患儿, 3个月, 入院前一天开始发热、呕 吐、水样便20+次/日,伴烦躁、烦渴。 查体:T 39.8℃,嗜睡,醒后烦躁,皮肤 弹性差,明显腹胀。 处理:庆大霉素抗感染,静脉点滴生理盐水 1200ml. 次日病情加重,极烦渴,呼吸深,惊厥, 昏迷,并发肠麻痹死亡。 Thank you