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 Acidosis
pH< 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:
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

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 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

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 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

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)

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 24
23
7
Acidosis Alkalosis
Coexistent Metabolic Alkalosis

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

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 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

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 (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 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 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

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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