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Macid and Malk


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Macid and Malk

  1. 1. An Approach to Metabolic Acidosis and Metabolic Alkalosis Presenter: Dr Abhay Pota Preceptor: Dr Deepika Singhal
  2. 2. Why Hydrogen ions, which are one millionth in concentration to that of Sodium, Potassium or Chloride in blood, are so important? The Permeability of a cell membrane to a given moiety is critically determined by the ionization of the substance. The ionization of the given substance in turn, is influenced by pH of its environment; if a substance exists in an ionized state its passage across the cell membrane will be considerably hindered. If a change in pH causes the substance to become relatively non-ionized, it will pass more freely across the cell membrane across its concentration gradient.
  3. 3. Metabolic Acidosis pH< 7.36 & HCO3 < 22mEq/L
  4. 4. Why Metabolic Acidosis is so important? • Cardiovascular:  Tachycardia with mild Metabolic acidosis  Impaired cardiac contractility  Increased risk of arrhythmias  Decreased cardiovascular responsiveness to catecholamines • Respiratory: Hyperventilation Vasoconstriction of pul vasculature Increased RV load>RV failure • Metabolic: Increased metabolic demands Reduction in ATP synthesis Hyperkalemia (secondary to cellular shifts) Increased protein degradation • Cerebral: Cerebral vasodilation>raised ICP
  5. 5. Anion Gap (AG) • Represents the concentration of unmeasured anions in the plasma • AG= Unmeasured anions- Unmeasured cations • To maintain electroneutrality, total number of cations should equal total number of anions [Na+] + UC = ([Cl-] + [HCO3-]) + UA UA-UC= [Na+] - ([Cl-] + [HCO3-]) • Normal: 12 ± 4mmol/L
  6. 6. Determinants of AG Unmeasured Anions Unmeasured Cations Albumin (15mEq/L) Calcium (5 mEq/L) Organic Acids (5 mEq/L) Potassium (4.5 mEq/L) Phosphate (2 mEq/L) Magnesium (1.5 mEq/L) Sulfate (1 mEq/L) ---------------------------- --------------------------- Total UA (23 mEq/L) Total UC (11 mEq/L) AG = UA – UC = 12 mEq/L
  7. 7. Anion Gap and Albumin • The normal AG is affected by patients plasma albumin concentration.  For every 1g/dl reduction in plasma albumin concentration the AG decreases by 2.5  Corrected AG = Calculated AG + [2.5 × (4 – albumin)]
  8. 8. High anion gap metabolic acidosis Causes  High anion gap (AG >12) 1) Lactic acidosis: Tissue hypoxia: Shock, Hypoxemia, Severe anemia Liver failure Malignancy Intestinal bacterial overgrowth Medications: Propofol 2) Ketoacidosis: Diabetic ketoacidosis,Starvation ketoacidosis,Alcoholic ketoacidosis Kidney failure 3) Poisoning: Ethylene glycol,Methanol,Toluene 4) Inborn errors of Metabolism
  9. 9. Pathogenesis • Retention of anions in plasma (increased anion gap): Overproduction of Acids – L-lactic acidosis  hypotension, shock, CCF, leukemia,other malignancies – Ketoacidosis (-hydroxybutyric acid) – Overproduction of organic acids in GI tract (D-lactic acidosis) – Conversion of alcohol (methanol, ethylene glycol) to acids – Organic acids in IEM
  10. 10. Non anion gap metabolic acidosis Causes Non-Anion Gap acidosis (Hyperchloremic Metabolic acidosis)  GI HCO3 loss - Diarrhoea - Ureterosigmoidostomy, , GI fistula, villous adenoma, ileal conduit  Renal acidosis - Hypokalemia – RTA 2/ RTA 1 - Hyperkalemia – RTA 4/ MC deficiency/ MC resistance - Tubulointerstitial disease
  11. 11. Actual Bicarbonate Loss Normal Plasma Anion Gap • Direct loss of NaHCO3 – Gastrointestinal tract (diarrhea, ileus, fistula, villous adenoma, ileal conduit ) – Urinary tract ( proximal RTA, use of carbonic anhydrase inhibitors) • Indirect loss of NaHCO3 – Low production of NH4 + (renal failure, hyperkalemia) – Low transfer of NH4 + to the urine (medullary interstitial disease)
  12. 12. Urinary Anion Gap • Differentiate cause of normal AG metabolic acidosis • Calculated as: UAG=UA-UC=(UNa+ + UK+)-UCl- • UAG (negative) = High NH4+, along with Cl-, excretion via kidney = (UNa+ + UK+)<UCl- = Gastrointestinal cause • UAG (positive) = Low NH4+, along with Cl-, excretion via kidney = (UNa+ + UK+)>UCl- = Renal Cause
  13. 13. Gap Gap  Gap gap = (measured AG – 12) / (24- measured HCO3) • If < 1, patient has an additional non-anion gap metabolic acidosis • If >1, patient has an additional metabolic alkalosis
  14. 14. Case Vignette 1 • For each 1 rise in anion gap, HCO3 should decrease by 1. • Patient with diarrhea and DKA • pH=7.08, Na=136, Cl= 110 and HCO3=5 • AG= 136- (110+5)= 21 • High AG metabolic acidosis • Normal AG=12, Excess AG=9 • Hence HCO3 should have fallen by 9 from 24 to 15 • But it is 5 (10 less than predicted) • Gap gap= (21-12)/(24-5) = 9/19 = <1 • 5 15 24 • 10 9 Acidosis Alkalosis Coexistent Metabolic
  15. 15. Case Vignette 2 • For each 1 rise in anion gap, HCO3 should decrease by 1. • pH=7.08, Na=143, Cl= 100 and HCO3=8 • AG= 143 - (100+10)= 35, (Normal AG=10±2) • Excess AG=23 • Hence HCO3 should have fallen by 23 (from 24 to 1) • But it is 8 (7 more than predicted) • Gap-gap= (35-12) / (24-8) = 23/16 = >1 1 8 24 23 7 Acidosis Alkalosis Coexistent Metabolic Alkalosis
  16. 16. Met Acidosis NAG  AG Ketones +ve  Serum Lactate  P Osm Gap (OH) B/AA = 5:1 (OH) B/AA = 3:1 +ve UAG - ve UAG Lactic AcidosisIntoxications(e.g. methanol) DKA Alcoholic GIT RTA Ketoacidosis < 5.5 Urine pH  K  K > 5.5 Type 1 Type 2 Type 4
  17. 17. Treatment • Indications of sodium bicarbonate use: • 1. Severe acidemia(pH<7.1) • 2. Hyperchloremic acidosis • 3. Mixed HAGMA & NAGMA • 4. HAGMA with non metabolizable anion in renal failure patient • Dose= 0.6 x wt in kg x Base Excess • Usually, half the dose of total is given over 2-4 hrs
  18. 18. Reasons for half correction • 1. Intracellular (paradoxical) acidosis especially in liver & CNS • 2. Bicarb fizzes with acid and causes respiratory acidosis- Considering that pCO2 of sodium bicarbonate is >200mm Hg, itreally is a CO2 burden(an acid load on the already acidotic body) that must be removed by the lungs • 3. Sodium bicarb contains sodium which causes hypernatremia>fluid overload • 4. Bicarbonate is not an effective buffer at physiological pH: Bicarb is generated from dissociation of H2CO3. Dissociation constant of H2CO3 is 6.1(i.e. pH at which 50% of acid is dissociated), and buffers are most effective within 1 pH unit on either side of pH. Therefore, bicarbonate is not expected to be an effective buffer at pH >7.1. • 5. Overcorrection- metabolic alkalosis-Hypokalemia • 6.  gut lactate production,  hepatic lactate extraction and thus  S. lactate
  19. 19. Other Therapeutics • Carbicarb -Used in Rx of met acidosis after cardiac arrest • THAM -More effective buffer in physiological range of blood pH Both drugs are not routinely available in india
  20. 20. Metabolic Alkalosis pH>7.44 & HCO3 > 26 mEq/L
  21. 21. Why Metabolic Alkalosis is so important? • Severe alkalemia (pH >7.6) can lead to increased binding of free calcium to albumin and hence decreased free blood calcium which impairs cardiac contractility • Alkalosis shifts O2-Hb dissociation curve to left, leading to decrease release of O2 to tissues • Decreased CO2 in CNS>Cerebral vasoconstriction>Depressed consciousness, seizures • Decreased ionised calcium> carpopedal spasms • Depression of respiratory system: • Hypoventilation • Decreased hypoxic drive
  22. 22. Causes of Metabolic Alkalosis CHLORIDE RESPONSIVE (urinary chloride <15 mEq/L) CHLORIDE UNRESPONSIVE (urinary chloride >20 mEq/L) Gastric losses (emesis or nasogastric suction) Diuretics (loop or thiazide) Chloride losing diarrhea Chloride deficient formula Cystic fibrosis Post hypercapnia Iv penicillin HIGH BLOOD PRESSURE Adrenal adenoma or hyperplasia Glucocorticoid remediable aldosteronism Renovascular disease Renin secreting tumor 17 α hydroxylase deficiency 11ß hydroxylase deficiency Cushing syndrome 11ß hydroxysteroid dehydrogenase deficiency Licorice ingestion Liddle syndrome NORMAL BLOOD PRESSURE Gitelman syndrome Bartter Syndrome Autosomal dominant hypoparathyroidism Base
  23. 23. Urinary classification of metabolic alkalosis • Why is this useful? -If urinary chloride is low, • The alkalosis is likely due to volume depletion • will respond to saline infusion -If urinary chloride is high, • Likely the alkalosis is due to hypokalemia or aldosterone excess • Will not respond to saline infusion
  24. 24. Generation stage • 1. loss of H+ - Vomiting or NG suction>loss of Hcl and hence H+ loss - Excess aldosterone>stimulates ENaC in CT>Na+ reabsorption>H+ secretion in exchange • 2. Shift of H+ intracellularly – in hypokalemia, k+ moves extracellularly> H+ moves in in exchange • 3. Contraction Alkalosis – diuretics cause fluid loss without bicarb, remaining bicarb is contained in smaller segment of water • 4. Alkali administration – Excess bicarb that overwhelms the capacity of kidneys
  25. 25. Maintenance Stage 1. Effective circulating volume depletion- Caused by either loss of fluid in vomiting or via diuretics stimulate aldosterone secretion via RAAS • Aldosterone directly enhances activity of the H+-ATPase pumps > promotes secretion of H+ into tubular lumen, increasing the reabsorption of bicarbonate. • Aldosterone-stimulated sodium reabsorption makes the lumen electronegative due to the loss of cationic Na+> H+ secretion in exchange 2. Chloride depletion - via loss of Hcl or via loss in urine via diuretics>decreased chloride delivery >diminishes bicarbonate secretion, as bicarb is secreted in exchange with cl
  26. 26. 3. Hypokalemia- • Fall in the plasma K+ concentration leads to a transcellular cation exchange: K+ moves out of the cells and electroneutrality is maintained by entry of extracellular H+ into the cells. • The ensuing intracellular acidosis can then stimulate hydrogen secretion and bicarbonate reabsorption • Distal hydrogen secretion is mediated by H-K-ATPase exchange pumps in the luminal membrane that actively reabsorb K+ as well as secreting H+.The activity of these transporters is appropriately stimulated by K+ depletion, thereby leading to a parallel increase in H+ secretion
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  28. 28. Management • Approach depends on the severity of the alkalosis and the underlying etiology. In children with a mild metabolic alkalosis ([HCO3 −] <32), intervention is often unnecessary. • 1. Cl sensitive: IV normal saline- volume expansion • Discontinue diuretics if possible • Gastric acid suppresants • 2. Cl resistant: Replace K+ if deficient • Acetazolamide • 3. Extreme Alkalemia: NH4Cl/Hcl infusion • Hemodialysis
  29. 29. Management • 1. Saline infusion: in Cl responsive alkalosis • Cl deficit= 0.2 * wt * (actual Cl- desired Cl) • Once the deficit is determined, infuse the volume of saline as: • Volume of saline(in litres)= Cl deficit/154 • 2. For patients with severe alkalemia, in whom saline infusion is contraindicated or has failed, 0.1 N Hcl can be transfused • H+ deficit= 0.5 * wt * (actual HCO3- desired HCO3) • Volume Hcl(in litres)= H+ deficit/100 • Because Hcl solutions are sclerosing, they must be infused via a large central vein and rate of infusion must be <0.2meq/kg/hr
  30. 30. Role of Gastric acid suppresants • Gastric acid suppression will substitute NaCl losses for Hcl losses so chloride will continue to be lost. • Considering that Cl depletion plays a major role in metabolic alkalosis resulting from GI losses, the rationale for gastric acid suppression needs to be reevaluated
  31. 31. Role of acetazolamide • Acetazolamide blocks HCO3 reabsorption in kidneys. The increase in HCO3 loss in urine is accompanied by increase in Na loss , producing diuretic effect. • So, useful in Chloride resistant cases and in patients with increased extracellular volume.
  32. 32.