macid and malk

An Approach to Metabolic Acidosis

and Metabolic Alkalosis

Presenter: Dr Abhay Pota

Preceptor: Dr Deepika Singhal

www.dnbpediatrics.com

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.


Metabolic AcidosispH< 7.36 & HCO3 < 22mEq/L


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


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


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


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)]


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


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


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


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)


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


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


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


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


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


Metabolic Alkalosis pH>7.44 & HCO3 > 26 mEq/L


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


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


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


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


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


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


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


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


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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