Chapter 4 Acid-base balance and acid-base disorders internal environment homeostasis Water balancehomeostasishomeostasisacid-base balanceacid-base balanceelectrolyte balance electrolyte balance 1. Acid-Base BalancelAcid-base BiochemistrylRegulation of pHlLaboratory Tests2. Simple Acid-base DisorderslMetabolic AcidosislRespiratory AcidosislMetabolic Alkalosis lRespiratory Alkalosis3. Mixed Acid-base Disturbance Contents Part I: Acid-base balance and its regulation lThe basic meaning of acid-base balance is the stable H+ in the body fluid. I、Concept of acid and baseacid ： An acid is a H+ donor, when it is dissolved in water. After the loss of H+, it becomes a base. HA (acid) H+ + A(base) H2CO3 H+ +HCO3 H2SO4, H3PO4base： A base is a H+ acceptor, when it is dissolved in water. After the combining of H+, it becomes an acid A(base)+ H+ HA (acid) HCO3 +H+ H2CO3 OH-, HCO3-, SO42-, HPO42-, NH3(I) Source of acidv volatile acidv fixed acidII、Sources of acid and baseThe main origin of acid and base is the intracellular metabolism (catabolism of protein, carbohydrate and fat). daily production ：300-400L/dExcretion:lungv 1.volatile acid H2CO3CO2 H2OH2CO3CAmetabolism of protein, carbohydrate and fatH+ + HCO3- Reabsorption in kidneyRBC、kidney tubulesepithelium 、alveolar epithelial cell 、gastric mucosa2. unvolatile acid (fixed acid) ： (50-100mmol/d) Uric acid, phosphoric acid (H3PO4) and sulfuric acid (H2SO4) are the products in the metabolic process of proteins and nuclear acids.Lactic acid and ketonic bodies (-hydroxybutyric acid and acetoacetic acid) can be formed from the metabolic process of carbohydrate and fat as intermediate products, when the oxygen supply is not sufficiency. Exogenous acid(food and drug)： Excretion through kidney (II) Sources of baseOrigin of baseslEndogenous： deaminationNH3 Less than acid productionlExogenous input： vegetables, and fruits III、 Regulation of acid-base balanceHenderson-Hasselbalch Equation Acid-base balance is mainly the balance between production and loss of acid and base. = 6.1 +1.3 = 7.4= 6.1 +1.3 = 7.4H+BufferRespiratoryRenalECFICF & bone(Immediately) ( 24h) (13min) (hs;13d)Neutralize H+paCO2 eH+ & iK+ exchangeExcrete H+Keep NaHCO3Acid-base balanceAcid-base balance ：pHpH pHpH SourceBuffer systemRespiratoryRenalCellular（I）blood buffer system表表1 1 全血五種緩沖系統(tǒng)全血五種緩沖系統(tǒng) 表表2 2 全血中各緩沖體系的含量與分布全血中各緩沖體系的含量與分布緩沖酸緩沖酸 緩沖堿緩沖堿 緩沖體系緩沖體系 占全血緩沖體系占全血緩沖體系% % H2CO3 HCO3 + H+ 血漿血漿HCO3 35H2PO4- HPO42 + H+ 紅細胞內(nèi)紅細胞內(nèi)Hb 18HPr Pr + H+ HbO2-及及Hb- 35HHb Hb + H+ 磷酸鹽磷酸鹽 5HHbO2 HbO2 + H+ 血漿蛋白血漿蛋白 7Buffer systemsBuffer systems ：consists of a weak acid and its saltHCOHCO3 3- -/H/H2 2CO3 is the most important buffer pair.CO3 is the most important buffer pair.vRegulate CO2 or HCO3- through kidney and lung， the most important buffer pair (50%)。vfixed acid and base buffer system HCO3-/H2CO3 buffer systemvPH is dermatied by HCO3-/H2CO3。 character: RBC specificity volatile acid buffer CO2CA：carbonic anhydrase CO2+H2O CA H2CO3 CA H+ HCO3- Cl- (RBC)HCO3-Cl-HHO2 HbO2-HHb Hb-hemoglobin buffer system (Hb-/HHb、HbO2-/HHbO2)phosphate buffer systemHPO42-/H2PO4-character: play a role in cell and kidneyprotein buffer systemPr/HPrIntracellular bufferMechanism of bufferHCl+NaHCO3NaCl+H2CO3CO2+H2O NaOH + H2CO3NaHCO3 + H2OAccept H+ or release H+ ，decrease the change of pHCharacter of Buffer Unvolatile acid：lHCO-3/H2CO3 system:l of the buffer capacitylOpened regulation: respiratory and renalVolatile acid ：lHb-/HHb、HbO2-/HHbO2（II）Mechanisms of respiratory controlchange the depth or rate of respiration change CO2 elimination HCO3-/ PaCO2 Acid-base balance1. central chemoreceptorPaCO2 (N:40mmHg) pH of CSF to stimulate central chemoreceptor the respiratory centerPulmonary ventilation volume PaCO2 60mmHg (8kPa) Pulmonary ventilation volume 10 times but, PaCO2 80mmHg (10.7kPa) inhibit respiratory center，named as carbon dioxide narcosis The central chemoreceptor is sensitive to the change of CO2, which is easy to cross the blood-brain barrier. It takes time for the H+ to penetrate across the blood brain barrier into the interstitial fluid of the brain, the increase of H+ in the brain is relatively slow, so the effect of H+ on the central chemoreceptor will be slow.central chemoreceptor2.peripheral chemoreceptorPaO2 、pH 、PaCO2 to stimulate peripheral chemoreceptor the respiratory center Pulmonary ventilation volume PaO2 60mmHg (8kPa) the respiratory center； but PaO2 30mmHg inhibit respirator center。Less sensitive than central chemoreceptor 3.Characteristic of respiratory compensation(a) Timeliness. The respiratory response begins within several minutes. The respiratory response often takes 30 minutes for the respiratory compensation. 1224 hours to get maximal compensation.（b) limited compensation(III) Renal regulation of acid-base Balance Renal compensation begins from several hours after the addition of acid load, and it may take 35 days to reach the maximum of this compensatory capacity. Kidneys play a major role in the regulation of pH in the body. Excrete the nonvolatile acid， reabsorb the bicarbonate ，“排酸保堿排酸保堿”keep keep HCOHCO3 3- - maintain acid-base balancemaintain acid-base balance。HCO3- filtrate through glomerulus freely（5000 mmol/d），），85%90% is reabsorbed by proximal tubule，others are reabsorbed by distal convoluted tubule and collecting duct，0.1% is excretedurine pH 6.0。 urine pH vary from 4.4 to 8.01.in proximal tubule(a) Na+-H+ exchange2.in distal tubule & collecting duct-intercalated cell: secrete H+ upper membrane: (a) H+-ATPase; (b) H+-K+ ATPaseUrinary acidification （H2PO4-NH4+） base membrane: Cl- /HCO3- exchange 3. secretion of NH3/NH4+ in proximal tubule4. competitive inhibition between K+-Na+ exchange and H+-Na+ in distal tubuleK+-Na+ exchange: secrete K+, reabsorb Na+，H+-Na+ exchange:secrete H+,reabsorb Na+acidosis， H+-Na+ exchange K+-Na+ exchangehyperkalemia。（IV) Cellular regulation(a) H+-K+ exchange(b) Cl- - HCO3- exchange(c) Utilizing of bone salt (d) Synthesis of urea from NH31. H+-K+ exchange 2. Cl- - HCO3- exchange When CO2 in ECF (serum) is increased, CO2 will move into the cells, CO2 combines H2O to form carbonic acid, then H2 CO3 dissociates to form H+ and HCO3 , the HCO3 moves out of the RBC, for neutrality, Cl moves into the cells. 3.Utilizing of bone salt In chronic metabolic acidosis, bone salt, Ca3(PO4)2, is also utilized as a buffer base, but the expense is decalcification of bone and osteoporosis (loose and soft bone). Ca3(PO4)2 + 4H+ 3 Ca2+ + 2 H2PO4 It is not a good way of regulating acid-base balance by utilization of bone salt.4.Synthesis of urea from NH3 in liver cellsSourceBuffer systemRespiratoryRenalCellularPart II laboratory tests of acid-base disturbances1. pH pH is the negative logarithm (-log) of H+ in a solution. H+=40nmol/L (pH=7.4) The normal range in artery blood =7.357.45 (7.41) The survival range of pH=6.87.8 According to the Henderson-Hasselbalch equation: 24 HCO3 metabolic factorpH =6.1+ log - 1.2 H2CO3 respiratory factors The primary changes determines the nature of the acid-base imbalance. The purpose of secondary change is to restore the pH. According to the pH:l compensatory acid-base disturbancesl decompensatory acid-base disturbancesClinical significance of PH(anticoagulant artery blood, insulation of air) A normal range of pH may represent three different situations: acid-base balance; compensatory acidosis or alkalosis; a mixed decompensatory acidosis and decompensatory alkalosis. Clinical significancepH7.45 decompensatory alkalosis (alkalemia) 2.PaCO2 (partial pressure of carbon dioxide in arterial blood) CO2 in blood: (a) 23% HbCO2 in RBC (b) 70% HCO3- in plasma (c) 7% CO2 molecule in plasma CO2 is determined by the rate of CO2 production and the rate of CO2 elimination. PaCO2 is the tension of CO2 caused by CO2 molecule movement. The normal range = 3346(40) mmHg (4.396.25 kPa). The capability of normal lung to eliminate CO2 is very good. CO2 retention will not occur with normal ventilation. Generally speaking, the PaCO2 is determined mainly by the respiration, so the PaCO2 is called the “respiratory factor”. Higher PaCO2 is due to the inhibition of respiration. Lower PaCO2 is due to overventilation. PaCO2Significance PaCO246mmHg Primary increase: respiratory acidosis Secodary increase: metabolic alkalosis (compensated by lung)PaCO2SB (CO2 retention), the reason must be the effect of respiratory factor, which indicates respiratory acidosis or metabolic alkalosis compensated by lung. If AB value predicted: with respiratory acidosis Value measured value predicted: with metabolic alkalosis Value measured 80 mmHg 6. treatment priciples(a) Treat the primary diseases which cause respiratory acidosis. (antibiotic, antispastic drugs) (b) Improve properly the ventilation.(c) Prevent from (respiratory alkalosis) over-ventilation during artificial respiration.（d) Be careful to alkaline drug(NaHCO3) THAMIII、 Metabolic alkalosisCharacterized by a primarily elevation in plasma HCO3- concentration and a high pH.1.concept 2.Classification According to the therapeutic effect of 0.9% NaCl, (A) saline-responsive alkalosis (B) saline-resistant alkalosis3. Pathogenesis(1) saline-responsive alkalosis(a) Increased loss of H+(b) More administration of HCO3 or precursors of bicarbonate(a) Increased loss of H+ a) from stomach There is a lot of H+ in the gastric juice. Vomiting and gastric suction will lose H+ HCO3- cl- is lost through gastric juice hypochloremic alkalosis HCO3- is absorbed into blood in stomach, then to intestinal juice to neutralize H+.Hypokalemia alkalosisEffective blood volumedecrease secondary aldosterone increaseSome diuretics (e.g. furosemide) can inhibit the reabsorption of Cl and Na+ in loop, more Na+ is reabsorpted with HCO3 (without Cl ) in distal tubules; renal fluid folw rate increase b) Increased loss H+ from kidneys (b) More administration of HCO3 or precursors of bicarbonatea) Patients with gastric ulcer may be orally given excessive NaHCO3 to neutralize gastric juice . b)Sharp correction of acidosis by excessive alkali administration can lead to metabolic alkalosis. c) Transfusion of anticoagulant blood with sodium citrate citrate. .(2) Chloride-resistant typePrimary hyperaldosteronism Secondary hyperaldosteronism caused by: hypovolemiaCushings syndrome severe hypokalemia:Paradoxical acid urine4.Compensation of metabolic alkalosis The compensation of metabolic alkalosis is the opposite direction of the compensation in metabolic acidosis. (1) ：H pulmonary ventilation volume CO2 elimination PaCO2 HCO3-/H2CO3(quickly,limted)But 46PaCO2 value predicted: with respiratory acidosisValue measured value predicted: with respiratory acidosis Value measured value predicted: with metabolic alkalosis Value measured value predicted: with metabolic alkalosis Value measured value predicted: with metabolic acidosis.Maximal compensatory value up to:12 mmol/L4.Changes of laboratory parameters(acute)pH PaCO2 SB() AB BB () BE ()HCO3- secondary decreaseH2CO3 primary decreaseincreaseChanges of laboratory parameters(chronic)pH PaCO2 SB AB BB -BEHCO3- secondary decreaseH2CO3 primary decreaseincrease5.Effect of respiratory alkalosis1. CNS dysfunction：GABA，cerebral blood flow 2. increased neuromuscular excitability(hypocalcemia ) tingling,twitching 3. hypokalemia4. hypophosphatemia6. treatment priciplesPrimary diseasePrevent mis-operation of mechanical ventilator5CO2 mixtrue gas inhalation or maskV. Mixed Acid-base DisturbancesConcept Metabolic acidosis, metabolic alkalosis, respiratory acidosis and respiratory alkalosis are four types of simple acid-base disturbance when these disturbances occur separately. A mixed acid-base disturbance is defined as the simultaneous co-existence of two or more simple disorders in the same patient. Double acid-base disorders Triple acid-base disorders Any two or three simple acid-base disturbances can occur simultaneously in a patient except the respiratory acidosis and respiratory alkalosis, because one can never have hypoventilation and hyperventilation at the same time. Mixed acid-base disturbances occur frequently as a part of severe underlying illness with a high mortality.Mixed Acid-base DisturbancesCase discussion A 45-year-old man had chronic cough for 20 years. He had a shortness of breath, orthopnea with edematous ankles for 1 month. The laboratory findings were: pH = 7.26 PaO2=55 mmHg PaCO2=60 mmHg AB = 22 mmol/L Predicted: HCO3- = 0.4x PaCO2 3 HCO3- = 24+0.4x 20 3=2935 Measured: 22pH reduced severely.No respiratory compensation for M. acidosisNo renal compensation for R. acidosis