macid and malk
TRANSCRIPT
An Approach to Metabolic Acidosis
and Metabolic Alkalosis
Presenter: Dr Abhay Pota
Preceptor: Dr Deepika Singhal
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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.
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Metabolic AcidosispH< 7.36 & HCO3 < 22mEq/L
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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:
HyperventilationVasoconstriction of pul vasculatureIncreased RV load>RV failure
• Metabolic:Increased metabolic demandsReduction in ATP synthesisHyperkalemia (secondary to cellular shifts)Increased protein degradation
• Cerebral:Cerebral vasodilation>raised ICP
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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
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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
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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)]
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High anion gap metabolic acidosisCauses
High anion gap (AG >12)
1) Lactic acidosis:
Tissue hypoxia: Shock, Hypoxemia, Severe anemiaLiver failureMalignancyIntestinal bacterial overgrowthMedications: Propofol
2) Ketoacidosis: Diabetic ketoacidosis,Starvationketoacidosis,Alcoholic ketoacidosisKidney failure
3) Poisoning: Ethylene glycol,Methanol,Toluene
4) Inborn errors of Metabolism
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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
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Non anion gap metabolic acidosisCauses
Non-Anion Gap acidosis (Hyperchloremic Metabolic acidosis)
GI HCO3 loss
- Diarrhoea
- Ureterosigmoidostomy, , GI fistula, villous adenoma, ilealconduit
Renal acidosis
- Hypokalemia – RTA 2/ RTA 1
- Hyperkalemia – RTA 4/ MC deficiency/ MC resistance
- Tubulointerstitial disease
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Actual Bicarbonate LossNormal 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)
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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
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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
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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 Acidosiswww.dnbpediatrics.com
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 2423
7
Acidosis Alkalosis
Coexistent Metabolic Alkalosiswww.dnbpediatrics.com
Met Acidosis
NAG
AGKetones +ve
SerumLactate
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
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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
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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 acidoticbody) 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. lactatewww.dnbpediatrics.com
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
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Metabolic Alkalosis pH>7.44 & HCO3 > 26 mEq/L
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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
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Causes of Metabolic Alkalosis
CHLORIDE RESPONSIVE (urinary chloride <15 mEq/L)
CHLORIDE UNRESPONSIVE (urinarychloride >20 mEq/L)
Gastric losses (emesis or nasogastricsuction)Diuretics (loop or thiazide)Chloride losing diarrheaChloride deficient formulaCystic fibrosisPost hypercapniaIv penicillin
HIGH BLOOD PRESSUREAdrenal adenoma or hyperplasiaGlucocorticoid remediable aldosteronismRenovascular diseaseRenin secreting tumor17 α hydroxylase deficiency11ß hydroxylase deficiencyCushing syndrome11ß hydroxysteroid dehydrogenasedeficiencyLicorice ingestionLiddle syndromeNORMAL BLOOD PRESSUREGitelman syndromeBartter SyndromeAutosomal dominant hypoparathyroidismBase Administrationwww.dnbpediatrics.com
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
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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
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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
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3. Hypokalemia-
• Fall in the plasma K+ concentration leads to a transcellularcation 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-ATPaseexchange 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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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
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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
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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
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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.
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