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 7.35 7.45 7.8 death acidosis alkalosis death 【H+】 160 40 16 nmol/L

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 [HCO-3] / [H2CO3] = 20:1

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.

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+ H2PO4- NH3 + 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. Moves Na+ and H+ in opposite directions. Normal urine normally is slightly acidic because the kidneys reabsorb almost all HC03- and 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. H2CO3 dissociates to HCO3- and H+. HCO3- generated within tubule cell diffuses into peritubular capillary.

Acidification of Urine

Na+ + HCO3- H+ H+ + HCO3- H+ H2CO3 CO2 + H2O H2CO3 H2O + CO2 HPO42-      H+ H+ + HCO3- H2CO3 CA H2O + CO2 H2CO3 HPO42- NH3 CA NH4 + H2PO4- 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+ H2PO4- NH3 + 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.

SB AB BB BE AB（即实际碳酸氢盐）：是指隔绝空气的全血标本，在实际状况下测得的血浆碳酸氢盐的量。（正常值为22-27mmol/L）。既是反映代谢因素的指标，又是反映呼吸因素的指标。 SB（即标准碳酸氢盐）：是指全血在标准条件（即温度在38℃，血红蛋白氧饱和度为100%，用PaCO2 40mmHg的气体平衡）下测得的血浆HCO3-含量。（正常值为22-27mmol/L，平均为24 mmol/L）。仅是反映代谢性因素的指标。但在慢性呼吸性碱中毒或慢性呼吸性酸中毒时，由于有肾脏代偿，也可以发生继发性降低或升高。 BB（即缓冲碱）：是指血液中所有具有缓冲作用的碱性物质的总和。（也就是血液中所有具有缓冲租用的负离子的总和，包括HCO3-，Hb-，Pr-等，正常值：45-52mmol/L）。是反映代谢因素的指标。 BE（即碱剩余）：是指在标准条件下，用酸或碱滴定全血标本至pH等于7.40时所需酸或碱的量（正常值：-3mmol/L~+3mmol/L）。是反映代谢因素的指标。正值增加碱过剩，负值增加碱缺失。

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

diarrhea; GI: intestinal suction (loss of intestinal fistula HCO-3) biliary fistula ② Metabolic acidosis in early renal failure: normal AG NH3 secretion H+ secretion Renal tubular acidosis: Kidney: depressant of C.A. (loss of acetazolamide (乙酰唑胺) HCO-3) intake of Cl- NaCl, 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 (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 (嗜睡), 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 (疲劳) CO2 narcosis (昏迷) 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

digestive tract vomiting; gastric suction(loss of HCl) ① loss diuretics distal flow rate of H+ (furosemide) blood volume Ald hyperaldosteronism H+-Na+exchange kidney H+-K+exchange between hypokalemia intra- and extra-cell renal secretion of H+ hypochloremia ②intake NaHCO3 of base transfusion of banked blood (citrate)

Gastric fluid loss and AB balance Blood vessel Gastric fluid loss and AB balance Esophagus Stomach Cl - Cl - Cl - H2CO3 HCO3- H+ H+ HCO3- H+ H2CO3 H+ HCO3- HCO3- Na+ Na+ Na+ Pancreas Duodenum

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 (焦虑) insanity (疯狂) pH brain-vessel dizziness(眩晕) contraction brain delirium O2 dissociation hypoxia Coma curve shifting to left ② neuromuscle pH free Ca2+ tic ③ hypokalemia arrhythmia

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 (抽搐) 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] respiration PaCO2 2) metabolic alkalosis plus respiratory alkalosis hepatic NH3 PaCO2 failure diuretic [HCO-3] 3) respiratory acidosis plus metabolic alkalosis pulmonary heart disease diuretic pH ± stop character pH character 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 7.56 (Normal: 35-45mmHg) PaCO2 50mmHg (Normal: 35-45mmol/L) SB 34mmol/L (Normal: 22-27mmol/L) BE 10mmol/L (Normal: -3.0-+3.0mmol/L) K+ 3.2mmol/L (Normal: 3.5-5.5mmol/L) Cl- 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]

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 其它 酸中毒 抑制性紊乱 血钾增高 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 酸中毒 抑制性紊乱 血钾增高 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(-)↑ [HCO3-] pH  PaCO2↓ [H+]

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 7.56 (Normal: 35-45mmHg) PaCO2 50mmHg (Normal: 35-45mmol/L) SB 34mmol/L (Normal: 22-27mmol/L) BE 10mmol/L (Normal: -3.0-+3.0mmol/L) K+ 3.2mmol/L (Normal: 3.5-5.5mmol/L) Cl- 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。

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