Acid base balance

1. ACID BASE BALANCE Dr Amith Sreedharan

2. DISCUSSION HEADINGS BASICS NORMAL PHYSIOLOGY ABNORMALITIES METABOLIC ACID BASE DISORDERS RESPIRATORY ACID BASE DISORDERS ALTERNATIVE CONCEPTS

3. Acid Any compound which forms H⁺ ions in solution (proton donors) eg : Carbonic acid releases H⁺ ions Base Any compound which combines with H⁺ ions in solution (proton acceptors) eg:Bicarbonate (HCO3 ⁻ ) accepts H+ ions

4. Acid–Base Balance Normal pH : 7.35-7.45 Acidosis Physiological state resulting from abnormally low plasma pH Alkalosis Physiological state resulting from abnormally high plasma pH Acidemia : plasma pH < 7.35 Alkalemia : plasma pH > 7.45

5. Henderson-Hasselbach equation (clinically relevant form) pH = p K a + log([HCO 3 - ]/.03xpCO 2 ) pH = 6.1 + log([HCO 3 - ]/.03xpCO 2 ) Shows that pH is a function of the RATIO between bicarbonate and pCO 2 PCO ₂ - ventilatory parameter (40 +/- 4) HCO₃⁻ - metabolic parameter (22-26 mmol /L)

6. ACIDS VOLATILE ACIDS: Produced by oxidative metabolism of CHO,Fat,Protein Average 15000-20000 mmol of CO₂ per day Excreted through LUNGS as CO₂ gas FIXED ACIDS (1 mEq /kg/day) Acids that do not leave solution ,once produced they remain in body fluids Until eliminated by KIDNEYS Eg : Sulfuric acid ,phosphoric acid , Organic acids Are most important fixed acids in the body Are generated during catabolism of: amino acids(oxidation of sulfhydryl gps of cystine,methionine ) Phospholipids(hydrolysis) nucleic acids

7. Response to ACID BASE challenge Buffering Compensation

8. Buffers First line of defence (> 50 – 100 mEq /day) Two most common chemical buffer groups Bicarbonate Non bicarbonate ( Hb,protein,phosphate ) Blood buffer systems act instantaneously Regulate pH by binding or releasing H⁺

9. Carbonic Acid–Bicarbonate Buffer System Carbon Dioxide Most body cells constantly generate carbon dioxide Most carbon dioxide is converted to carbonic acid, which dissociates into H + and a bicarbonate ion Prevents changes in pH caused by organic acids and fixed acids in ECF Cannot protect ECF from changes in pH that result from elevated or depressed levels of CO 2 Functions only when respiratory system and respiratory control centers are working normally Ability to buffer acids is limited by availability of bicarbonate ions

10. Acid–Base Balance The Carbonic Acid–Bicarbonate Buffer System

11. The Hemoglobin Buffer System CO 2 diffuses across RBC membrane No transport mechanism required As carbonic acid dissociates Bicarbonate ions diffuse into plasma In exchange for chloride ions ( chloride shift ) Hydrogen ions are buffered by hemoglobin molecules Is the only intracellular buffer system with an immediate effect on ECF pH Helps prevent major changes in pH when plasma P CO 2 is rising or falling

12. Phosphate Buffer System Consists of anion H 2 PO 4 - (a weak acid )(pKa-6.8) Works like the carbonic acid–bicarbonate buffer system Is important in buffering pH of ICF Limitations of Buffer Systems Provide only temporary solution to acid–base imbalance Do not eliminate H + ions Supply of buffer molecules is limited

13. Respiratory Acid-Base Control Mechanisms When chemical buffers alone cannot prevent changes in blood pH, the respiratory system is the second line of defence against changes. Eliminate or Retain CO₂ Change in pH are RAPID Occuring within minutes PCO₂ ∞ VCO₂/VA

14. Renal Acid-Base Control Mechanisms The kidneys are the third line of defence against wide changes in body fluid pH. movement of bicarbonate Retention/Excretion of acids Generating additional buffers Long term regulator of ACID – BASE balance May take hours to days for correction

15. Renal regulation of acid base balance Role of kidneys is preservation of body’s bicarbonate stores. Accomplished by: Reabsorption of 99.9% of filtered bicarbonate Regeneration of titrated bicarbonate by excretion of: Titratable acidity (mainly phosphate) Ammonium salts

16. Renal reabsorption of bicarbonate Proximal tubule: 70-90% Loop of Henle : 10-20% Distal tubule and collecting ducts: 4-7%

17. Factors affecting renal bicarbonate reabsorption Filtered load of bicarbonate Prolonged changes in pCO2 Extracellular fluid volume Plasma chloride concentration Plasma potassium concentration Hormones (e.g., mineralocorticoids, glucocorticoids)

18. If secreted H + ions combine with filtered bicarbonate, bicarbonate is reabsorbed If secreted H + ions combine with phosphate or ammonia, net acid excretion and generation of new bicarbonate occur

19. NET ACID EXCRETION Hydrogen Ions Are secreted into tubular fluid along Proximal convoluted tubule (PCT) Distal convoluted tubule (DCT) Collecting system

20. Titratable acidity Occurs when secreted H + encounter & titrate phosphate in tubular fluid Refers to amount of strong base needed to titrate urine back to pH 7.4 40% (15-30 mEq ) of daily fixed acid load Relatively constant (not highly adaptable)

21. Ammonium excretion Occurs when secreted H + combine with NH 3 and are trapped as NH 4 + salts in tubular fluid 60% (25-50 mEq ) of daily fixed acid load Very adaptable (via glutaminase induction)

22. Ammonium excretion Large amounts of H + can be excreted without extremely low urine pH because pK a of NH 3 /NH 4 + system is very high (9.2)

23. Acid – Base Balance Disturbances Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH.

24. Acid – Base Balance Disturbances Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH. decreased

25. Four Basic Types of Imbalance Metabolic Acidosis Metabolic Alkalosis Respiratory Acidosis Respiratory Alkalosis

26. Acid Base Disorders Disorder pH [H + ] Primary disturbance Secondary response Metabolic acidosis    [HCO 3 - ]  pCO 2 Metabolic alkalosis    [HCO 3 - ]  pCO 2 Respiratory acidosis    pCO 2  [HCO 3 - ] Respiratory alkalosis    pCO 2  [HCO 3 - ]

27. Metabolic Acidosis Primary AB disorder ↓HCO₃⁻ → ↓ pH Gain of strong acid Loss of base(HCO₃⁻)

28. ANION GAP CONCEPT To know if Metabolic Acidosis due to Loss of bicarbonate Accumulation of non-volatile acids Provides an index of the relative conc of plasma anions other than chloride,bicarbonate [serum Na⁺ - (serum Cl ⁻ + serum HCO₃⁻)] Unmeasured anions – unmeasured cations 8 – 16 mEq /L (5 – 11,with newer techniques) Mostly represent ALBUMIN

29. Concept of Anion Gap

30. Back

31. CAUSES OF METABOLIC ACIDOSIS ( High anion gap ) →( Normochloremic ) LACTIC ACIDOSIS KETOACIDOSIS Diabetic Alcoholic Starvation RENAL FAILURE ( acute and chronic) TOXINS Ethylene glycol Methanol Salicylates Propylene glycol

32. Normal anion gap( Hyperchloremic ) MET.ACIDOSIS causes Gastrointestinal bicarbonate loss A. Diarrhea B. External pancreatic or small-bowel drainage C. Ureterosigmoidostomy , jejunal loop, ileal loop D. Drugs 1. Calcium chloride (acidifying agent) 2. Magnesium sulfate ( diarrhea ) 3. Cholestyramine (bile acid diarrhea ) Renal acidosis A. Hypokalemia 1. Proximal RTA (type 2) 2. Distal (classic) RTA (type 1) B. Hyperkalemia Drug-induced hyperkalemia (with renal insufficiency) A. Potassium-sparing diuretics ( amiloride , triamterene, spironolactone) B. Trimethoprim C. Pentamidine D. ACE-Is and ARBs E. Nonsteroidal anti-inflammatory drugs F. Cyclosporine and tacrolimus Other A. Acid loads (ammonium chloride, hyperalimentation ) B. Loss of potential bicarbonate: ketosis with ketone excretion C. Expansion acidosis (rapid saline administration)

33. URINE NET CHARGE/UAG Distinguish between hyperchloremic acidosis due to DIARRHEA RTA UNC= Na⁺+ K⁺- Cl ⁻ Provides an estimate of urinary NH₄⁺ production Normal UAG = -25 to -50 Negative UAG – DIARRHEA( hyperchloremic acidosis) Positive UAG – RTA

34. “DELTA RATIO” / “GAP-GAP” Ratio between ↑in AG and ↓in bicarbonate (Measured AG – 12):(24 – measured HCO₃⁻) To detect another metabolic ACID BASE disorder along with HAGMA ( nagma / met.alkalosis ) HAGMA(NORMOCHLOREMIC ACIDOSIS) :- RATIO = 1 HYPERCHLOREMIC ACIDOSIS (NAGMA):- RATIO < 1 In DKA pts,after therapy with NS Met.acidosis with Met.alkalosis :- RATIO > 1 Use of NG suction and DIURETICS in met.acidosis pt FIG

35. Compensation for Metabolic acidosis H + buffered by ECF HCO 3 - & Hb in RBC; Plasma Pr and Pi: negligible role (sec-min ) Hyperventilation – to reduce PCO ₂ ↓pH sensed by central and peripheral chemoreceptors ↑ in ventilation starts within minutes,well advanced at 2 hours Maximal compensation takes 12 – 24 hours Expected PCO₂ calculated by WINTERS’ FORMULA EXP.PCO₂ =1.5 X (ACTUAL HCO₃⁻ )+8 +/- 2 mmHg Limiting value of compensation: PCO₂ = 8-10mmHg Quick rule of thumb : PCO₂ = last 2 digits of pH

36. Acid–Base Balance Disturbances . Responses to Metabolic Acidosis

37. Metabolic acidosis Symptoms are specific and a result of the underlying pathology Respiratory effects: Hyperventilation CVS: ↓ myocardial contractility Sympathetic over activity Resistant to catecholamines CNS: Lethargy,disorientation,stupor,muscle twitching,COMA , CN palsies Others : hyperkalemia

38. Metabolic Alkalosis ↑ pH due to ↑HCO₃⁻ or ↓acid Initiation process : ↑in serum HCO₃⁻ Excessive secretion of net daily production of fixed acids Maintenance: ↓HCO₃⁻ excretion or ↑ HCO₃⁻ reclamation Chloride depletion Pottasium depletion ECF volume depletion Magnesium depletion

39. CAUSES OF METABOLIC ALKALOSIS I. Exogenous HCO3 − loads A. Acute alkali administration B. Milk-alkali syndrome II. Gastrointestinal origin 1. Vomiting 2. Gastric aspiration 3. Congenital chloridorrhea 4. Villous adenoma III. Renal origin 1. Diuretics 2. Posthypercapnic state 3. Hypercalcemia / hypoparathyroidism 4. Recovery from lactic acidosis or ketoacidosis 5. Nonreabsorbable anions including penicillin, carbenicillin 6. Mg2+ deficiency 7. K+ depletion

40. Chloride responsive alkalosis Low urinary chloride concentration (<15 meq /L) Gastric acid loss Diuretic therapy Volume depletion Renal compensation for hypercapnea Chloride resistant alkalosis Elevated urinary chloride (>25 meq /L) 1 ⁰ mineralocorticoid excess Severe pottasium depletion A/W volume expansion

41. Compensation for M etabolic A lkalosis Respiratory compensation: HYPOVENTILATION ↑PCO ₂= 0.6 mm  pCO 2 per 1.0 mEq /L ↑HCO 3 - Maximal compensation: PCO ₂ 55 – 60 mmHg Hypoventilation not always found due to Hyperventilation due to pain due to pulmonary congestion due to hypoxemia(PO ₂ < 50mmHg)

42. Acid – Base Balance Disturbances . Metabolic Alkalosis

43. Metabolic Alkalosis Decreased myocardial contractility Arrythmias ↓ cerebral blood flow Confusion Mental obtundation Neuromuscular excitability Hypoventilation pulmonary micro atelectasis V/Q mismatch(alkalosis inhibits HPV)

44. Contraction Alkalosis Loss of HCO₃⁻ poor, chloride rich ECF Contraction of ECF volume Original HCO₃⁻ dissolved in smaller volume ↑HCO ₃⁻ concentration Eg : Loop diuretics/Thiazides in a generalised edematous pt.

45. Respiratory Acidosis ↑ PCO ₂ → ↓pH Acute(< 24 hours) Chronic(>24 hours )

46. RESPIRATORY ACIDOSIS - CAUSES CNS DEPRESSION DRUGS:Opiates,sedatives,anaesthetics OBESITY HYPOVENTILATION SYNDROME STROKE NEUROMUSCULAR DISORDERS NEUROLOGIC:MS,POLIO,GBS,TETANUS,BOTULISM,HIGH CORD LESIONS END PLATE:MG,OP POISONING,AG TOXICITY MUSCLE:↓K⁺,↓PO₄,MUSCULAR DYSTROPHY AIRWAY OBSTRUCTION COPD,ACUTE ASPIRATION,LARYNGOSPASM

47. CONT.. CHEST WALL RESTRICTION PLEURAL: Effusions, empyema,pneumothorax,fibrothorax CHEST WALL: Kyphoscoliosis , scleroderma,ankylosing spondylitis,obesity SEVERE PULMONARY RESTRICTIVE DISORDERS PULMONARY FIBROSIS PARENCHYMAL INFILTRATION: Pneumonia, edema ABNORMAL BLOOD CO₂ TRANSPORT DECREASED PERFUSION: HF,cardiac arrest,PE SEVERE ANEMIA ACETAZOLAMIDE-CA Inhibition RED CELL ANION EXCHANGE: Loop diuretics, salicylates, NSAID

48. Compensation in Respiratory Acidosis Acute resp.acidosis : Mainly due to intracellular buffering( Hb,Pr,PO ₄) HCO₃⁻ ↑ = 1mmol for every 10 mmHg ↑ PCO ₂ Minimal increase in HCO₃⁻ pH change = 0.008 x (40 - PaCO ₂) Chronic resp.acidosis Renal compensation (acidification of urine & bicarbonate retention) comes into action HCO₃⁻ ↑= 3.5 mmol for every 10 mm Hg ↑PCO₂ pH change = 0.003 x (40 - PaCO ₂) Maximal response : 3 - 4 days

49. Acid – Base Balance Disturbances Respiratory Acid–Base Regulation.

50. RS: Stimulation of ventilation ( tachypnea ) dyspnea CNS: ↑cerebral blood flow → ↑ICT CO₂ NARCOSIS ( Disorientation,confusion,headache,lethargy ) COMA(arterial hypoxemia,↑ ICT,anaesthetic effect of ↑ PCO₂ > 100mmHg) CVS: tachycardia,bounding pulse Others: peripheral vasodilatation( warm,flushed,sweaty )

51. Post hypercapnic alkalosis In chronic resp.acidosis Renal compensation → ↑HCO₃⁻ If the pt intubated and mechanical ventilated PCO ₂ rapidly corrected Plasma HCO₃⁻ doesn’t return to normal rapidly HCO₃⁻ remains high

52. Respiratory Alkalosis Most common AB abnormality in critically ill ↓PCO ₂ → ↑pH 1⁰ process : hyperventilation Acute : PaCO ₂ ↓,pH- alkalemic Chronic: PaCO ₂↓,pH normal / near normal

53. CAUSES OF RESPIRATORY ALKALOSIS A. Central nervous system stimulation 1. Pain 2. Anxiety, psychosis 3. Fever 4. Cerebrovascular accident 5. Meningitis, encephalitis 6. Tumor 7. Trauma B. Hypoxemia or tissue hypoxia 1. High altitude 2. Septicemia 3. Hypotension 4. Severe anemia C. Drugs or hormones 1. Pregnancy, progesterone 2. Salicylates 3. Cardiac failure D. Stimulation of chest receptors 1. Hemothorax 2. Flail chest 3. Cardiac failure 4. Pulmonary embolism E. Miscellaneous 1. Septicemia 2. Hepatic failure 3. Mechanical ventilation 4. Heat exposure 5. Recovery from metabolic acidosis

54. Compensation for respiratory Alkalosis Acute resp.alkalosis : Intracellular buffering response-slight decrease in HCO₃⁻ Start within 10 mins ,maximal response 6 hrs Magnitude: 2 mmol /L↓HCO₃⁻ for 10 mmHg↓PCO ₂ LIMIT : 12-20 mmol /L ( avg =18) Chronic resp.alkalosis : Renal compensation (acid retention,HCO ₃⁻ loss) Starts after 6 hours , maximal response 2- 3 days Magnitude : 5mmol/L ↓HCO₃⁻ for 10mmHg ↓PCO₂ LIMIT : 12-15 mmol /L HCO ₃⁻

55. Acid–Base Balance Disturbances Respiratory Acid–Base Regulation.

56. Respiratory alkalosis CNS : ↑ neuromuscular irritability( tingling,circumoral numbness) Tetany ↓ ICT(cerebral VC) ↓CBF(4% ↓ CBF per mmHg ↓PCO ₂) Light headedness,confusion CVS: CO& SBP ↑ (↑ SVR,HR) Arrythmias ↓ myocardial contractility Others: Hypokalemia,hypophosphatemia ↓ Free serum calcium Hyponatremia,hypochloremia

57. Acid Base Disorders Primary disorder Compensatory response Metabolic acidosis PCO ₂=1.5 X (HCO₃⁻) + 8 +/₋ 2[Winter’s formula] Metabolic alkalosis 0.6 mm  pCO 2 per 1.0 mEq /L  HCO 3 - Acute respiratory acidosis 1 mEq /L  HCO 3 - per 10 mm  pCO 2 Chronic respiratory acidosis 3.5 mEq /L  HCO 3 - per 10 mm  pCO 2 Acute respiratory alkalosis 2 mEq /L  HCO 3 - per 10 mm  pCO 2 Chronic respiratory alkalosis 5 mEq /L  HCO 3 - per 10 mm  pCO 2

58. STRONG ION APPROACH Metabolic parameter divided into 2 components “STRONG” acids and bases Electrolytes, lactate,acetoacetate,sulfate “WEAK” buffer molecules Serum proteins and phosphate pH calculated on the basis of 3 simple assumptions Total concentrations of each of the ions and acid base pairs is known and remains unchanged Solution remains electroneutral Dissociation constants of each of the buffers are known Both pH and bicarbonate are dependent variables that can be calculated from the concentrations of “ STRONG ” and “ WEAK ” electrolytes and PCO₂

59. STRONG ION DIFFERENCE ( SID ) STRONG CATIONS – STRONG ANIONS Decrease in SID → Acidification of PLASMA Explains – NS induced ACIDOSIS ADV : Estimate of H⁺ conc more accurate than Henderson Hasselbalch equation. DIS ADV :Complex nature of equations,increased parameters limit clinical application

60. BASE EXCESS/DEFICIT Base excess and base deficit are terms applied to an analytical method for determination of the appropriateness of responses to disorders of acid-base metabolism by measuring blood pH against ambient PCO2 and against a PCO2 of 40 mmHg deficit is expressed as the number of mEq of bicarbonate needed to restore the serum bicarbonate to 25 mEq /L at a PCO ₂ of 40 mmHg compared with that at the ambient PCO ₂ misleading in chronic respiratory alkalosis or acidosis physiological evaluation of the patient be the mode of analysis of acid-base disorders rather than an emphasis on derived formulae

61. ACID BASE NORMOGRAM

62. MIXED ACID BASE DISORDER Diagnosed by combination of clinical assessment , application of expected compensatory responses , assessment of the anion gap, and application of principles of physiology. Respiratory acidosis and alkalosis never coexist Metabolic disorders can coexist Eg : lactic acidosis/DKA with vomiting Metabolic and respiratory AB disorders can coexist Eg : salicylate poisoning ( met.acidosis + resp.alkalosis )

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