ACID BASE DISORDER

1. “ Acid Base Imbalance” author Dr.Praveen Pawal Jr. medicine m.l.b .medical college jhansi.u.p Seminar Department of Medicine MLB Medical College, Jhansi

5. Basic terminology pH – signifies free hydrogen ion concentration. pH is inversely related to H + ion concentration. Acid – a substance that can donate H + ion, i.e. lowers pH. Base – a substance that can accept H + ion, i.e. raises pH. Anion – an ion with negative charge. Cation – an ion with positive charge. Acidaemia – blood pH< 7.35 with increased H + concentration. Alkalaemia – blood pH>7.45 with decreased H + concentration. Acidosis – Abnormal process or disease which reduces pH due to increase in acid or decrease in alkali. Alkalosis – Abnormal process or disease which increases pH due to decrease in acid or increase in alkali.

7. Regulation of acid base The regulation of pH in a narrow range is the function of buffers, lung and kidney. The Henderson – Hasselbalch equation describes the correlation between metabolic and respiratory regulations, which maintains pH. Buffers – Buffers are chemical systems which either release or accept H + . So, buffers minimize change in pH induced by an acid or base load and provide immediate defense, but have least buffering power. e.g. – bicarbonate, bone bicarbonate, proteins, phosphate, Hb. Respiratory regulation – by excreting volatile acids, lungs regulate PaCO 2 . When amount of CO 2 increases in body , it will stimulate PaCO 2 sensitive chemoreceptors at central medulla, with resultant rise in rate and depth of breathing. pH = 6.1+log HCO 3 - PaCO 2 ×0.0301

8. This hyperventilation will maintain PaCO 2 at normal range. Respiratory regulation acts rapidly (in seconds to minutes) and has double buffering power as compared to chemical buffers. CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 - HbH  H + + Hb HCO 3 - Tissue CO 2 Venous Blood Cl -

9. HCO 3 - O 2 Alveolar capillary barrier Cl - O 2 + HbH  HbO 2 + H + H + + HCO 3 -  H 2 o + CO 2 Lung

17. Normal ABG Values -: Na + 135-145meq/lt K + 3.5-5.5meq/lt TCO 2 21-30meq/lt iCa 1.1-1.4mmol/lt HCT 47 + 7% (male) 42 + 5% (female) Hb 13.5-17.5 (male) 12-16 (female) At 37°C pH 7.35-7.45 PCO 2 40±5mmHg PO 2 95±5mmHg HCO 3 - 24±2 mEq/lt BE etc ±2 mEq/lt SPO 2 97 ۬ ±2%

19. TCO 2 :- Total CO 2 content of plasma is the sum of the plasma concentration of HCO 3 - , dissolved CO 2 and H 2 CO 3 . The contribution of CO 2 and H 2 CO3 is small. Hence, total CO 2 in plasma and HCO 3 concentration are often used interchangeably. Base excess :- is derived from whole blood buffer base, defined as sum of concentration of buffer anions (HCO 3 - and Hb) in whole blood. BE is defined as difference between the observed and normal values for whole blood buffer base. It is used to overcome the limitation of plasma HCO 3 - as an index of acid base status.

21. B ase excess = 0.93 ( HCO 3 - 24.4 + 14.8(pH - 7.4)) Alternatively expressed: Base excess = 0.93 HCO 3 + 13.77 pH - 124.58 Van Slyke equation--

22. SO 2 :- Percent of O 2 attached to Hb PaO 2 :- Pressure with which O 2 is dissolved in blood. 90% 60 mmHg 10% PaO 2 SO 2 Oxygen Dissociation Curve – Sigmoid shaped curve

27. Common causes of type 2 respiratory impairment Chronic obstructive pulmonary disease Opiate /benzodiazepine toxicity Exhaustion Inhaled forein body Flail chest injury Neuromuscular disorders Kyphoscoliosis Obstructive sleep apnoea The ABG in different pattern of type 2 impairment Paco2 HCo3 Ph Acute ↑ -> ↓ Chronic ↑ ↑ -> Acute on chronic ↑ ↑ ↓

28. A-a gradient The A-a gradient is the difference between the po 2 in alveoli (PAo 2 ) and the Po 2 in aterial blood (Pao 2 ). Pao 2 is measured on ABG but PAo 2 has to be calculated using the alveolar gas equation A-a gradient = PAo 2 - Pao 2 It is normally less than 2.6 kpa (20 mmHg), although it increases with age and Fio2 .This means that : 1.the normal range for Pao2 falls with age 2.the A-a gradient is most accurate when performed on room air. Simplefied alveolar gas equation PAo2 (kpa) = (Fio2 x 93.8)-(Paco2 x 1.2) Or PAo2 (mmHg) = (Fio2 x 713)-(Paco2 x 1.2) Assumes the patient is at sea level and has a body temperature of 37°

30. Compensation – The body’s response to neutralize the effect of the initial insult on pH homeostasis is called compensation. pH Primary change Secondary change Metabolic acidosis Low HCO 3  PaCO 2  Metabolic alkalosis High HCO 3  PaCO 2  Respiratory acidosis Low PaCO 2  HCO 3  Respiratory alkalosis High PaCO 2  HCO 3 

31. Rule of same direction :- In simple acid base disorders, HCO 3 and PaCO 2 compensatory change are in the same direction as the primary changes.  HCO 3 leads to  PaCO 2  HCO 3 leads to  PaCO 2 This will bring pH to near normal although not to normal. If these changes are in opposite direction or the actual changes are not equal to expected, it suggests mixed disorder.

32. 2-Metabolic alkalosis (  HCO 3 )- Rise in PaCO 2 =0.75x Rise in HCO 3 3-Respiratory acidosis   PaCO 2 )-- Acute - Rise in HCO 3 =0.1x Rise in PaCO 2 Chronic - Rise in HCO 3 = 0.4x Rise in PaCO 2 4-Respiratory alkalosis   PaCO 2 )--- Acute - Fall in HCO 3 =0.2x Fall in PaCO 2 Chronic - Fall in HCO 3 = 0.4x Fall in PaCO 2 1-Metabolic acidosis (  HCO 3 )– Expected PaCO 2 = (1.5 × HCO 3 - ) +8 OR PaCO 2 = HCO 3 - + 15

33. By calculating compensation, we can differentiate between simple and mixed disorder. If expected change = actual change, disorder is simple If actual change is more or less than predicted, disorder is mixed. Mixed disorder :- defined as independent coexistence of more than one primary acid base disorder. Most common is mixed metabolic acidosis and respiratory acidosis.

44. ABG Ph 6.95 PCo 2 23.9mm Hg P0 2 45mmHg Bicarb 5.3 mmol/l BE -27 S0 2 55% K 2.2 mmol/l Na 140 mmol/l Cl 118 mmol/l iCa+ 0.87 Hb 11.9 gm /dl

55. Case 3 Date :02/04/09 Patient Name : Smt Kranti 26yrs Female Case of type 1 DM diagnosed 4 months back had discontinued medication from 1 month. Came here with C/C - 1-Fever x 2 day 2-Pain in knee joint x 2 days 3-Breathlessness x 2 day PR- 110/min BP -100/ 70mm Hg RR 30/min Dehydration++ Investigations--- RBS >500 mg Ketone: large Sugar : ++++ S.creat. :1.10 mg/dl TLC : 24,100/cmm

57. ABG 02/04/09 Ph 6.99 PCo 2 10.5 mmHg P0 2 111 mmHg BE -29 mmol/L HCo3 2.6 Tco2 45 SO2 95 Na+ 138 mmol/L K+ 4.2 mmol/L iCa+ 1.06 mmol/L Hb 12.6 g/dl

59. Management DKA with severe metabolic Acidosis with respiratory alkalosis. 1- IV Antibiotics 2- HCO3 Deficity Calculated --- =O.5 X (BW) (actul HCO 3 - DesiredHCO 3 ) =0.5 x 40x 12.3 = 247 Meq/L (11 amp of sodabicarb) out of which half is given with in 2 hr & rest to be given over 24 hrs IV. 3- Inj insulin R accordingly to RBS. 4- IVF : NS ISO -M

60. 03/04/09 Ph 7.462 PCo 2 30.1 mmHg P0 2 107mmHg BE -2 mmol/L HCo3 21.6 Tco2 15 So2 96 Na+ 138.6 mmol/L K+ <2.0 mmol/L iCa+ 1.0 mmol/L Hb 12.1 g/dl

61. Next day ABG was repeated pt had mild(metabolic Acidosis with Respiratory alkalosis) with hypokalemia may because of i/v NAHCO3 & insulin both of which causes intracellular shift of potassium .Hypokalemia was corrected. Pt improved.

62. Case 4 Pt Pyarelal 20 yrs old admitted here on 31 st August 2009 with complain of snake bite in night with features of respiratory muscles paralysis. Pt was immediately intubated and put on mechanical ventilation. After resumption of spontaneous breathing pts ABG was done on next day at 3:52 PM to decide wheather to wean off from ventilator or not. Pt’s ABG was -----

65. Ans Pts pH is normal i.e.7.42 PCO2 is normal i.e. 39.9 HCO3 is within normal range i.e.26 PO2 is 75 mm Hg It means pt’s ABG is normal except decrease PO2 .So pt can be weaned of from ventilator after assessing the clinical condition and supplemental O2 should be given by mask On assessing it was seen that pt was properly breathing with full effort and depth, RR is 16/min, pt was weaned off from ventilator in the evening and put on T-Tube breathing with supplemental oxygen, pt survived.

66. Case 5 Pt Ramchandra 29 yrs/male admitted here with complain of 10-12 loose motions per day with passage of blood along with fever for 3 days, for 1 day he also c/o decreased amount of urine. For all these he was admitted here and managed on the lines of acute gastroenteritis with ARF. On next day of admission he develops breathlessness with deterioration in his condition for which ABG was done which shows-

69. Analysis of ABG Pt is pH is 7.46 ie alkalosis, pCO2 is 19. So it is Respiratory alkalosis. For acute Resp. alkalosis--- Fall in HCO3- =0.2 X Fall in PaCO2 = 0.2 x (40-19) =0.2 X 21=4.2 so expected HCO3 = 24-4.2 = 19.8 but actual HCO3=13.5 which is less then the expected. So it is mixed disorder with metabolic acidosis due to hypoperfusion , renal failure, lactic acidosis due to sepsis and loss of HCO3 during diarrhea with Resp. alkalosis due to hyperventilation because of sepsis.

70. Case 6 58 years old male Gyasi admitted to Hospital with C/C -- 1-Fever chills and rigor x 8 days 2-Altered sensorium x 4 hrs 3-Breathlessnes x 4 hrs 4-Decreased urine output O/E : Pt unconscious PR- 90/min BP -70 systolic RR- 28 /min INVESTIGATION: Sr creatnine: 13.50 mg /dl Hb:4.80 g/dl TLC :27,200/cmm P-90 L-03 QBC-Negative

72. ABG Na + 139 K+ 5.3 Tco 2 0.65 Hb 5.0 PH 6.798 Pco 2 10 Po 2 120 HCO 3 1.5 BE -30 SO 2 93%

74. Amount of sodabicarb to be given ---- =(Desired HCO 3 - Actual HCO3) X 0.5X BW =(10-1.5) x 0.5 x 50 =212 (about 12 amp of SBC to be given ,out of which half of dose should be given in 1 st hr & rest over next 24 hrs ). Management --- BT II ⨀ Antibiotic Antimalarial Antihyperkalemic Peritoneal Dialysis was planned Patient expired before intervention was done.

75. Case 7 Name : Vandana 23 yrs ,Female k/c/ o pul koch’s four times defaulter(CAT II) Came her with C/C --- Breathlessness at rest O/E : Pt nutrition was poor and malnourished PR- 100/min BP- 100/70 mmHg Chest : B/L crepts X-ray : Rt side pnemothorax localised with extensive b/l infiltration. TLC -8900 P-83 L-14 E-2 Sr.crt : 1.0mg/dl Sr .billirubin : 0.64mg/dl SPO2 : 66 %

76. ABG Na+ 134 K+ 3.5 Tco 2 27 ica 0.86 HCt 37 Hb 12.6 Ph 7.516 Pco 2 31.8 Po 2 36 Hco 3 25.2 BE 3 m mol/L So 2 65 %

78. Management ---- High flow oxygen Therapy IV Antibiotics ATT as advised by DOTS.

79. Case 8 Biharilal 60 yrs male. Admitted as case of Pul koch’s with Syst HTN was taking ATT & Amlong H. C/C : 1- low grade fever 2- ↓ Appetite 3- Lethargy O/E: PR-92/min regular BP :150/90 mm Hg Chest :: B/L crepts ++ Dehydration ++

82. pH: 7.449 So alkalosis HCO3 is 26.8 Primary disorder is metabolic Alkalosis. So expected rise in Paco2= 0.75X Rise in HCO 3 = 0.75X2.8 = 2.1 So expected paco2= 40+2.1 = 42.1 so it is mixed disorder ie metabolic alk alosis with ECF volume depletion due to thiazide diuretics and Respiratory alkalosis due to hyperventilation with hyponatrimia with hypokalemia.

86. ABG 07/08/09 PH 7.27 PCo 2 17.9 P0 2 101 BECF -20 HCo 3 6.6 Tco 2 7 So 2 97 Na+ 124 K+ 2.78 iCa+ 0.25 Cl- 108

89. Case10 History A 25 year old man, with no significant past medical history. Presents to the emergency department with a 2-day history of fever, productive cough and worsening breathlessness. Examination He is hot and flushed with a temperature of 39.3ºC. He does not appear distressed but is using accessory muscles of respiration. There is diminished chest expansion on the left with dullness to percussion, bronchial breathing and coarse crakles in the left lower zone posteriorly. Pulse 104 beats/min Respiratory rate 28 breaths/min Blood pressure 118/70 mmHg SaO 2 89%

90. H+ 31.8 nmol/L Ph 7.50 PCo 2 3.74 kPa 28.1 mmHg P0 2 7.68 kPa 57.8 mmhg Bicarb 23.9 mmol/L BE -0.5 mmol/L SP0 2 88.7% Lactate 1.2 K 3.7 mmol/L Na 138 mmol/L Cl 99 mmol/L iCa+ 1.2 mmol/L Hb 15 g/dl

91. Answer:- This patient has moderate type 1 respiratory impairment. Hyperventilation is an appropriate response to the hypoxaemia and sensation of dyspnoea and has resulted in a mild alkalaemia (remember that metabolic compensation does not occur in response to acute respiratory acid-base disturbance). The correct management for his condition is supplemental oxygen to correct the hypoxaemia and appropriate antibiotics to treat the infection. In a patient such as this, with moderate hypoxaemia and no ventilatory impairment, monitoring by pulse oximetry is more appropriate than repeated than repeated ABG sampling. Indications for further ABG analysis would include signs of exhaustion or hypercapnia or a further significant decline in Sao 2 .

99. METABOLIC ACIDOSIS IN SPECIFIC SITUATION [ I ] Increased Anion Gap Acidosis 1. Lactic acidosis It is the most serious and most common cause of metabolic acidosis in hospitalized critically ill patients. The most common cause of lactic acidosis is shock (cardiogenic or septic) Type A - Characterized by impaired tissue oxygenation. Type B - No hypoxia but mitochondrial respiration is impaired.

100. Causes of lactic acidosis Diagnosis – Diagnose lactic acidosis in increased AG acidosis, by exclusion of ketoacidosis, intoxication, renal failure. Serum lactate levels confirm the diagnosis. Normal S. lactate level – 1mEq/lt Lactic acidosis – 4-5mEq/lt Commonly goes upto - 10-30mEq/lt. Type A Type B Shock (Cardiogenic or septic) Respiratory failure Carbon monoxide or Cyanide poisoning Severe anaemia Diabetes mellitus Hepatic failure Severe infection Toxins – Ethanol, Methanol Drugs - Biguanides

101. Treatment Goal of therapy is adequate tissue oxygenation and treatment of the underlying cause. Tissue oxygenation can be improved by high inspired oxygen fraction, ventilator support, repletion of ECF volume, after load reducing agents and inotropic support by dopamine and dobutamine. Avoid vasoconstricting drugs like noradrenaline, as they can worsen tissue hypoxia. Administration of NaHCO 3 is started late (pH <7.1) and discontinued early. Early bicarbonate hemodialysis is effective.

102. 2 . Diabetic ketoacidosis Due to overproduction of acetoacetic acid and  -hydroxybutyric acid due to relative or absolute insulin deficiency. Cornerstone of treatment is insulin administration, with replacement of water, Na + and K + . Alkali should not be administered routinely as insulin and supportive therapy regenerate bicarbonate from resolution of retained ketone bodies. Bicarbonate is indicated in patients where pH<7.1, the goal of therapy is to raise pH to relatively safe level of 7.2. HCO 3 is also indicated in severe hyperkalemia.

103. 3. Alcoholic ketoacidosis It occurs after abrupt discontinuation of alcohol consumption and is usually due to vomiting, prolonged starvation and volume depletion. Correction of hypoglycemia with dextrose infusion will stimulate insulin secretion and inhibit glucagon secretion and thereby promote regeneration of bicarbonate from metabolism of retained ketone bodies. Correction of hypovolemia will prevent ketoacidosis. Supplement thiamine with glucose to avoid development of Wernicke’s encephalopathy.

105. Thus, unless blood is already alkalinzed by respiratory alkalosis, give NaHCO3 infusion – 88mEq/4amp of NaHCO3 in 1 lt of D5% and infuse at rate of 10-15 ml/kg/hr. (25ml of 7.5% NaHCO3 contains 22mEq NaHCO3). Bicarbonate haemodialysis can be done in patients with serum concentration of salicylates > 80mg /dl, refractory acidosis, severe CNS symptoms, progressive clinical deterioration, pulmonary edema, renal failure.

106. 5. Renal failure At gfr <20ml/min, inability to excrete H+ with retention of anions – PO 4 3- , SO 4 2+ results in increased anion gap acidosis. The unmeasured anions replace HCO3 - which is consumed as a buffer. Hyperchloremic metabolic acidosis (normal anion gap) develops in milder cases (gfr = 20-50ml/min). Correction of severe acidosis with alkali therapy in renal failure patients carries risk of volume overload. In such patients, dialysis can be used.

107. II ] Normal anion gap acidosis The hallmark of this disease is low HCO 3 of metabolic acidosis with hyperchloremia so that anion gap remains normal 1. GI loss of bicarbonate Diarrhea or pancreatic damage can result in HCO 3 loss due to increased secretion and decreased absorption. Hyperchloremia occurs because the ileum and colon secrete HCO 3 - in one to one exchange for Cl - by counter transport. The resultant volume contraction causes further increased Cl - retention by kidney in setting of decreased HCO 3 . Correction of hypvolemia and hypokalemia are the most important measures. Correction of acidosis with NaHCO 3 is required only in selected patients with severe acidosis.

108. 2. Renal tubular acidosis a. Classic distal (type 1) RTA Characterized by hypokalemic, hyperchloremic metabolic acidosis and is due to selective deficiency of H + secretion in distal tubules. Despite acidosis, Urinary pH is always above 5.5 Nephrocalcinosis, nephrolithiasis and bone disease are important clinical complications. Supplementation of bicarbonate (1-3mEq/kg/day) is essential. Potassium salt is given to correct hypokalemia.

109. b. Proximal (type 2) RTA characterized by hypokalemic, hyperchloremic metabolic acidosis due to a selective defect in proximal tubular ability to reabsorb filtered HCO 3 . During early stage, when HCO 3 is >18 mEq/lt, urine is alkaline but can be acidic when plasma HCO 3 <15-18 mEq/lt. Treatment is to treat the underlying disorder. If alkali therapy is needed, dose is quite large (10-15mEq/lt). Supplement potassium adequately to avoid hypokalemia. Thiazide diuretics can also be helpful.

110. c. Type IV RTA It is characterised by a disturbance in distal nephron function that impairs renal excretion of both H + and K + , so there is hyperchloraemic normal anion gap acidosis with hyperkalemia. Magnitude of hyperkalemia and acidosis are disproportionately severe for the observed degree of renal insufficiency. In Type IV RTA, mild to moderate chronic renal failure is almost always present. Urine pH can be <5.5. Urinary ammonium excretion is depressed.

111. Urinary anion gap to assess hyperchloremic metabolic acidosis – Metabolic acidosis   NH 4 Cl excretion by the kidney Urinary anion gap reflects the ability of the kidney to excrete NH 4 Cl. Urinary anion gap = Na + + K + - Cl - 80 - NH 4 + Normally urinary anion gap is zero or positive with a value of 30-50 (mmol/lt). It is useful to differentiate between gi and renal cause of hyperchloremic acidosis. If the cause is gi HCO 3 loss, urinary anion gap is negative because of increased NH 4 Cl excretion by kidney. In RTA, with impaired NH 4 Cl excretion, urinary AG is positive.

112. In contrast to urinary NH 4 + excretion, measurement of urine pH cannot reliably distinguish acidosis of renal or extrarenal origin. An acidic urine pH does not necessarily indicate increase in net acid excretion. With a significant reduction in the availability of ammonium to serve as a buffer, only a small amount of distal H + secretion will lead to a maximal reduction in urine pH. In this setting, pH of the urine is acidic but the quantity of H + excretion is insufficient of meet daily acid production. By contrast, alkaline urine doest not necessarily imply a renal acidification defect. In conditions where availability of NH 4 + is not limiting, distal H + secretion can be massive and yet the urine remains relatively alkaline due to buffering effects of NH 4 + .

114. Causes of Metabolic Alkalosis Saline responsive (Urine chloride <15 mEq/L) Saline resistant (Urine chloride > 20mEq/L) ECF volume depletion Vomiting / Gastric suction Diuretics Hypercapnia correction No ECF vol. Depletion NaHCO 3 infusion Multiple transfusion Normal or increased ECF Vol Hypertensive Hyperaldosteronism Cushing’s syndrome Normotensive Bartter’s syndrome Severe K + depletion

117. 6. Dialysis can be useful in occasional patients with severe metabolic alkalosis, volume overload and renal failure. C. Saline resistant – Specific treatment of underling cause like surgical treatment for pituitary tumour or adrenal adenoma, or supportive treatment, like spironolactone, correction of hypokalemia, sodium restriction.

119. Causes of Respiratory Acidosis CNS depression Drugs (anesthesia, sedative) Infection, Stroke Neuromuscular impairment Myopathy, myasthenia gravis, polymyositis, hypokalemia Ventilation restriction Rib fracture, pneumothorax, haemothorax Airway Obstruction, asthma Alveolar diseases COPD, pulmonary oedema, ARDS, pneumonitis Miscellaneous Obesity, hypoventilation

122. B. Oxygen therapy Oxygen therapy is like a “Double edged Sword”. In acute respiratory acidosis, major threat to life is hypoxia and not hypercapnia. So O 2 supplementation is needed. In chronic hypercapnia, O 2 therapy should be instituted cautiously and in lowest possible concentration since hypoxia may be primary and only stimulus to respiration. C. Mechanical ventilation In acute respiratory acidosis, early use of mechanical ventilator is more appropriate. While in chronic respiratory acidosis, more conservative approach is admirable, because of greater difficulty in weaning such patients from ventilators.

124. D. Alkali therapy Avoid alkali therapy except in patients with associated metabolic acidosis, severe acidaemia (pH<7.15), severe bronchospasm, as alkali therapy restores responsiveness of bronchial musculature to  agonists. Respiratory alkalosis  PaCO 2 ­  pH (>7.45) Etiology Respiratory alkalosis is the most frequently encountered acid base disorder

126. Clinical features Clinical features vary with severity, rate of onset and underlying disorder. The mortality increase is in direct proportion to the severity of hypocapnia. PaCO 2­ below 20-25 mmHg carries a grave prognostic sign, specially in critically ill patients. Common features are :- Light headache, tingling of the extremities, circumoral anaesthesia, cardiac arrhythmias, tetany or seizures.