1. Chapter 4(1) Acid – Base Disorders §1. Acid- Base balance 1.Concept of acid and base Acid: Acid is a proton donor. (HCl, NH 4 + ) HCl → H + + Cl - NH 4 + → H + + NH 3 Base: Base is a proton acceptor. (OH -, HCO 3 -, NH 3 ) OH - + H + → H 2 O HCO 3 - + H + → H 2 CO 3 NH 3 + H + → NH 4 +

2. 2.Origins of acid and base in the body Source of acid: 1) origins of volatile acid It results from an end-product of oxidative metabolism namely CO 2. CO 2 +H 2 O = H 2 CO 3 Normally produced CO 2 300-400 L/d or H + 15 mol/d. 2) origins of nonvolatile acid ( fixed acid ) It comes from metabolic processes or incomplete oxidation of glucose or fats and so on. as: H 2 SO 4, H 3 PO 4, lactic acid, acetoacetic acid, β-hydroxybutyric acid.

3. Sulfuric acid: Catabolism of sulfur-containing amino acids. Sulfuric acid: Catabolism of sulfur-containing amino acids. Phosphoric acid; Catabolism of phosphoesters,phosphoprotein,nucleotide. Lactic acid: Incomplete oxidation of carbohydrate. Beta-hydroxybutyric acid, acetoacetic acid: Incomplete oxidation of fatty acid. Incomplete oxidation of fatty acid. Normally produced H + 50-100 mmol/d. Normally produced H + 50-100 mmol/d.

4. 3) Exogenous acid intake Salicin intoxication Hydrochloric acid

5. Origin of bases: 1) NH 3 : It is formed by deamination of amines, amino acid, purines and so on. 2) Eatting salt of organic acid: Sodium citratc and sodium lactate come from vegetable and fruits.

6. 3. Regulation of acid – base balance 1) Chemical buffers: Buffer system is composed by weak acid and weak acid salt. It may convert strong acid into weak acid or strong alkali into weak alkali. NaHCO 3 +HCl → NaCl+H 2 CO 3 H 2 CO 3 +NaOH → H 2 O+NaHCO 3

7. Major buffer system in the body Carbonic acid/Bicarbonate(HCO 3 - /H 2 CO 3 ) : The major extracellular buffer ， regulated by lungs and kidneys ， effective ， determining the pH of plasma. Phosphate (HPO 4 2- /H 2 PO 4 - ) : Intracellular Protein (Pr - /HPr) : Plasma/Intracellular Hemoglobin (Hb - /HHb and HbO 2 - /HHbO 2 ) : RBC *A buffer system cannot buffer itself.  fast / no permanence

8. 2) Respiratory control: Expelling more CO 2 through respiration→to exclude volatile acid. H + →chemoreceptor → excite respiratory centre → hyperventilation → exclude volatile acid  Fast / effectively / only excludes volatile acid

9. l PaCO 2  (40-80 mmHg)  Blood-brain barrier permeable to CO 2 : CO 2 +H 2 O  H 2 CO 3  H + +HCO 3 - (in cerebrospinal fluid, CSF)  [H + ]   Central chemoreceptor(beneath the ventral surface of the medulla oblongata)  Respiratory center   Ventilation  (Main) PCO 2   80 mmHg, inhibition of respiratory center. PCO 2   80 mmHg, inhibition of respiratory center. PaO 2  (30-60 mmHg) /pH  / PCO 2  Peripheral chemoreceptor (Carotid bodies, aortic bodies)  Respiratory center  Ventilation  (Minor) PaO 2  (30-60 mmHg) /pH  / PCO 2  Peripheral chemoreceptor (Carotid bodies, aortic bodies)  Respiratory center  Ventilation  (Minor) Pa O 2   30 mmHg, inhibition of respiratory center Pa O 2   30 mmHg, inhibition of respiratory center

10. 3) Role of kidney (exclusion of acid with conservation of base) hydrogen ion secreted ammonium excreted by renal tubular cell bicarbonate reabsorbed  Effectively ( fixed acid may be excluded ) / slowly

11. Role of the kidneys powerfully, slowly # Proximal tubule: H + secretion coupled with HCO 3 - reabsorption # Collecting tubule H + secretion and excretion coupled with the addition of new HCO 3 - to the plasma Secreted ammonia once the normal urinary phosphate buffers are saturated. NH 3 + H +  NH 4 +

12. 4) Role of tissue and cell cell: intra and extra ions exchange across the cellular membrane buffering in the cell or titrating base in ECF Decalcification, osteoporosis. bone: Ca 3 (PO 4 ) 2 +4H + 3Ca 2+ +2H 2 PO 4 Decalcification, osteoporosis. Effectively / but need time Effectively / but need time

13. Acid-base balance: acid-base balance Acid and bases are continuously produced in the body, PH is maintained 7.35-7.45 by four regulation of the body, This condition is termed as acid-base balance.

14. pH=  log [H + ]=log1/ [H + ] (The logarithm to the base 10 of the reciprocal of the [H + ]) §2. Laboratory parameters of acid-base balance 1. PH ： pH=  log [H + ]=log1/ [H + ] (The logarithm to the base 10 of the reciprocal of the [H + ]) HCO 3 - (metabolic factor) pH= pKa+ log ——————————— H 2 CO 3 (respiratory factor) = pKa + logHCO 3 - /α×PCO 2 ＝ 6.1+1.3=7.4 Normal plasma pH 7.35-7.45 ( average 7.4 ) Normal plasma pH 7.35-7.45 ( average 7.4 )

15. 2. PaCO 2 ( respiratory parameter ): Partial pressure of CO 2 dissolved in arterial plasma( Normal range: 4.39~6.25kPa(33~46mmHg) Average: 5.32kPa(40mmHg) Partial pressure of CO 2 dissolved in arterial plasma( The pressure is produced by CO 2 dissolved in arterial plasma). Normal range: 4.39~6.25kPa(33~46mmHg) Average: 5.32kPa(40mmHg) PaCO 2 ＞ Normal (hypoventilation) a.primary change: RAC b.secondary change: MAL with respiratory compensation PaCO 2 ＜ Normal (hyperventilation) a.primary change: RAL b.secondary change: MAC with respiratory compensation

16. Average : 24 m mol/L 3. SB AB BB BE (metabolic parameter): SB: HCO 3 - in plasma under standard condition 22~27 mmol/L AB: HCO 3 - in plasma under actual condition 22~27 mmol/L Average : 24 m mol/L BB: BB = HCO 3 - + Pr - + Hb - 45~55 mmol/L BE: BE = ΔBB = BB-NBB -3~+3 mmol/L MAC: primary decreased MAL: primary elevated

17. Normal condition : PaCO 2 ＝ 5.32Kpa( 40mmHg ) 24 mmol/L ( average) AB ＝ SB ＝ 24 mmol/L ( average) AB ＞ SB → CO 2 retention: RAC (primary change) MAL with respiratory compensation AB ＜ SB → CO 2 expiration:RAL (primary change) MAC with respiratory compensation AB↑ ＝ SB↑→ MAL without respiratory compensation

18. 4. AG( anion gap ): AG=UA(undetermined anion – UC(undetermined cation ) [HCO 3 - ]+[Cl - ]+UA= [Na + ]+UC AG =UA-UC=[Na + ]-([HCO 3 - ]+[Cl - ])=140-(24+104)=12mmol/L±2

19. §3. Simple acid-base disorder 1. Metabolic acidosis 1) concept: primary disturbance [HCO 3 - ] ↓ ; PH. AB↓, SB↓, BB↓, BE ↓ ; PaCO 2 ↓ ; AB ＜ SB 2) clasification: Normal AG MAC High AG MAC 3) pathogenesis and mechnisms: (1) lose of bases (2) gaining acids

20. Metabolic acidosis Metabolic acidosis Causes: Causes: (1) lose of bases (bicarbonate decreased) Gastrointestinal losses: diarrhea, fistulae and so on. Renal losses: proximal renal tubular acidosis and distal renal tubular acidosis Gastrointestinal losses: diarrhea, fistulae and so on. Renal losses: proximal renal tubular acidosis and distal renal tubular acidosis Lactic acidosis: tissue hypoxia, impaired oxygen utilization, severe liver dysfunction, and shock Ketoacidosis: diabetic,hepatic cirrhosis, alcoholic poisoning, or starvation Renal failure: conservation of acids (2) gaining acids (bicarbonate consumed in buffering) Lactic acidosis: tissue hypoxia, impaired oxygen utilization, severe liver dysfunction, and shock Ketoacidosis: diabetic,hepatic cirrhosis, alcoholic poisoning, or starvation Renal failure: conservation of acids Exogenous acid intake: ammonium chloride, salicylate, ethylene glycol(commonly used in antifreeze), or methanol intoxication Exogenous acid intake: ammonium chloride, salicylate, ethylene glycol(commonly used in antifreeze), or methanol intoxication

21. Compensation Effects 4) Compensation: all regulation system take part in 5) Effects: (1) Depression of central neural system a Elevated activities of glutamate decarboxylase →GABA ↑ Treatment b.ATP ↓ (2) Depression of heart and vessel(Ca 2+ transport disorder; hyperkalemia;ATP↓): cardiac output ↓ ; cardiac arrhythmias; peripheral vasodilation. (3) Skin: warm and flashed ( 4 ) Alteration of skeleton: decacification, retarding growth and osteodystrophy 6) Treatment: administration of 5%NaHCO 3, sodium lactate, THAM.

22. Concept Classification Respiratory acidosis 1) Concept: Primary change : retention of CO 2 ; pH. PaCO 2 ↑ ; AB↑ SB↑ BB ↑ BE ↑ ; AB ＞ SB 2) Classification: Acute RAC Chronic RAC

23. Causes 3) Causes : Disorder of external respiration - Overdosage of sedatives, narcotics,etc. Cerebrovascular accidents. Cardiopulmonary arrest Central nervous system trauma, infections Poliomyelitis Inhalation of foreign bodies Chronic obstructive pulmonary disease Asthma Pneumonia Increased CO 2 inhalation – Misoperation of mechanical ventilator Inhalation CO 2 of high concentration

24. Compensation 4) Compensation: In acute RAC: ion exchange across the membrane and buffering in cell

25. HCO 3 - + H + H + +A - HA K + 体细胞（ somatic cell ） CO 2 +H 2 O H 2 CO 3

26. Red blood cell CO 2 CO 2 +H 2 O H 2 CO 3 H + +Hb - HHb + HCO 3 - - Cl -

27. In chronic RAC: excretion of more H + and ammonia ion reabsorption of more HCO 3 - in kindneys

28. Effects 5) Effects: (1) Neurological effects: CO 2 narcosis (2) Cardiovascular effects: arrhythmias; pulmonary artery hypertension; cardiac output decrease. (3) Mixed acid-base imbalance (RAC+MAC) (4) Inducting of hyerkalemia and hypochloremia 6) principle of treatment: improve ventilation

29. Concept Metabolic alkalosis 1) Concept: Primary disturbance [HCO 3 - ] ↑ ; PH. AB↑, SB↑, BB↑, BE↑; PaCO 2 ↑ ; AB ＞ SB Classification: 2) Classification: Chloride – responsive MAL Chloride – resistant MAL

30. Causes and mechanism Mechanism 3) Causes and mechanism: Mechanism: a. Excessive gain of alkali (bicarbonate) b. Excessive loss of hydrogen ions, chloride or potassium ions

31. Causes: a Causes: a.Excessive gain of alkali (bicarbonate) Bicarbonate intake:treatment of MAC citrate-containing blood transfusions Parenteral solution containing lactate b b.Excessive loss of hydrogen ions, chloride or potassium ions Gastrointestinal H+ loss:vomiting,gastric suction Renal H+ loss:Aldosteronism,cushing’s syndrome thiazide and loop diuretic potassium deficit c c.Volume contraction Dehydration Diuretic therapy

32. Compensation Effects 4) Compensation: Blood buffer role limitation Respiratory regulation Ion exchange and H + out cell to titrate bicarbonate Renal role: excluding bicarbonate and conserving H + 5) Effects: (1) Hypoventilation→ PaCO 2 ↑, PaO 2 ↓ (2) Agitation of central neural system: GABA↓ → seizures (3) Increase excitability of the neuromuscle: free [Ca 2+ ] decrease → muscle tremors (4) Mental dysfunction: O 2 dissociated curve leftshift → impairing O 2 release → ATP ↓. At 6-8 hs, 2,3-DPG  and curve shifts back towards the right. (5) Hypokalemia → reduced fibrillation threshold

33. Principle of treatment 6) Principle of treatment: a. Etiology treatment b. Replacing N.S or NH 4 Cl solution. c. Administration of KCl. or spironolactone if K + and Cl - deficits are present d. Carbonic anhydrase inhibitor: acetazolamide

34. Respiratory alkalosis Concept 1) Concept: Primary change : H 2 CO 3 ↓ or PaCO 2 ↓ ; pH. PaCO 2 ↓ ; AB↓ SB↓ BB↓ BE↓ ; AB<SB Classification 2) Classification: a. Acute RAL b. Chronic RAL

35. Causes and mechanisms Mechanisms: Causes: 3) Causes and mechanisms: Mechanisms: Hyperventilation Causes: a. Psychogenic hyperventilation:Hysteria b. Stimulation of respiratory center: High altitude hypooxia Salicylate toxication Blood ammonia↑(Hepatic encephalopathy) Encephalitis Brain injury Fever c. Inappropriately high ventilator settings

36. Compensation Effects Principle of treatment 4) Compensation: In acute RAC: Ion exchange, H + out of cell to titrate base in ECF In chronic RAC: Decreased excretion of H + and NH 4 + Decreased reabeorption of HCO 3 - 5) Effects: (1) Increased excitability of the nerve and muscle (2) Mental dysfunction (3) Hypokalemia,hypochloridemia 6) Principle of treatment: a. Decreased ventilation by administration of sedative. b. Application of a plastic bag to inspire more amount of CO 2 gas

37. Parameter changes of simple types Disorder Primary Change Second Response pH Disorder Primary Change Second Response pH Metabolic acidosis HCO 3 -  PaCO 2  pH  Respiratory acidosis PaCO 2  HCO 3 -  pH  Metabolic alkalosis HCO 3 -  PaCO 2  pH  Respiratory alkalosis PaCO 2  HCO 3 -  pH  Compensated X ： after compensation, pH still in normal. Uncompensated X ： after compensation, pH still abnormal.

38. §4. Mixed acid –base disturbance Definition : more than one primary acid-base disorder coexist in a patient. Double disorders 1) MAC+RAC: diabetic ketosis with pulmonary disease 2) MAL+RAL: vomiting with hyperventilation 3) MAC+RAL: uremia with high fever 4) MAL+RAC: diuretics with respiratory failure 5) MAC + MAL: heart failure with hypokalemia

39. Triple disorders : respiratory acidosis + MAC + MAL respiratory alkalosis

40. §5. Diagnosis 1. According to pathogensis establishing primary change 2. Manifestation: excitation — alkalosis inhibition — acidosis 3. According to PH PH 7.45 — alkalemia — alkalosis PH=7.35~7.45: normal condition complete compensation mixed acid-base disturbance 4. Condition of compensation:direction ； predicted compensative value ； compensative limit 5. Estabolilshed triple disorders: utilized AG

41. The patient was suffered from salicylate intoxication. His blood- gas parameters (lab. Value): PH = 7.45 PaCO 2 = 2.6 kpa (20mmHg) HCO 3 - =13mmol/ L.what acid-base disorders presented in this patient ? Causes: salicylate intoxication. Primary change is HCO 3 - decreased. HCO 3 - =13mmol/L<24mmol/L MAC pH: pH=7.45=N compensated MAC mixed acid-base imbalance (MAC+RAL) Compensatory condition: PaCO 2 =2.6kpa(20mmHg)<5.32kpa(40mmHg) Calculate: 1.2×ΔHCO 3 ±2=1.2 ×(24-13) ±2=13.2 ±2=11.2-15.2 Predicted PaCO 2 value =40 - (11.2or15.2)=24.8-28.8mmHg Actual PaCO 2 =20mmHg < predicted PaCO 2 =24.8 –28.8mmHg diagnosis: MAC+RAL