Metabolic Alkalosis
Metabolic Alkalosis - Overview
Introduction
1.
1.
2. Renal handling of
Bicarbonate
3. Causes of Metabolic
Alkalosis
4. Consequences
5. Compensation
6. Diagnostic Approach
7. Management
Metabolic alkalosis - Introduction
Primary acid base disorder due to loss of H or
+
gain of HCO3 in ECF
-
Rise in the HCO3 is noted (>) along with rise in
-
pH(>)
Rise in pH leads to Hypoventilation - Secondary
rise in Arterial CO2 tension (PaCO2)
Hence Metabolic alkalosis is characterised by
coexisting rise of arterial pH, serum HCO3 and
-
PaCO2
Often associated with Hypochloremia and
Hypokalemia
Metabolic alkalosis - Introduction
Metabolic alkalosis accounts for % of
hospitalized children with acid-base disorder
A direct relationship between mortality and
arterial pH exists when pH >
Mortality rates
Major adverse effects of alkalemia is seen when
pH >
Renal handling of Bicarbonate
Metabolic alkalosis = Gain of base or loss of acid
Regulation of Bicarbonate by kidney
Reabsorption of filtered HCO3- Production of new HCO3-
By excreting H+
Titratable acid Excretion of NH4+
Reabsorption of Bicarbonate
Freely
filtered
Reabsorption of Bicarbonate in Proximal
tubule
Regulation of Bicarbonate in Proximal
tubule
pH at the end of Proximal tubule = 6.5 - 6.8
Mutations in CAII - Mixed Proximal and Distal Renal
Tubular Acidosis with Osteopetrosis
Mutations in Na - HCO3 Cotransporter - Proximal
+ -
Renal Tubular Acidosis
Cl - HCO3 exchanger - Basolateral membrane
- -
Reabsorption of Bicarbonate in Proximal Tubule
gets affected by ECF volume status
Adrenergic agonists, Angiotensin II and
Hypercalcemia stimulates HCO3 reabsorption
-
Parathyroid hormone inhibits HCO3 reabsorption
-
Regulation of Bicarbonate in Proximal
tubule
Metabolic alkalosis with
Volume contraction Edematous states
(eg., Vomiting)
Decreased effective
arterial volume
Activation of
hormones
to maintain ECF
(Catecholamines, Angiotensin II, Aldosterone)
High HCO reabsorption along with Na
3
- +
Maintains metabolic alkalosis till volume is corrected
Acidification in Distal nephron
Secretion of H into the lumen
+
Mainly occurs in Intercalated cells (contains CA)
α-IC(TypeA) cells secrete H and β-IC(TypeB) cells
+
secrete HCO3 -
Acidification in Distal nephron
Mutations in AE-1 or apical H -ATPase or in its
+
subunit domains (V0 transmembrane domain and
V1 cytosolic domain) - Distal Renal Tubular
Acidosis
Apical H /K - ATPase - Useful in cases of
+ +
potassium depletion
Distal tubule - HCO3 exit the cell across the
-
basolateral membrane and secretion of H into the
+
lumen
Ammonia excretion
Proximal tubule
Glutamine -
Precursor of NH3
Chronic acid
base status and
Potassium levels
alters the
production of
ammonium
Causes of Metabolic Alkalosis
Failure of kidney to eliminate HCO3 at the normal capacity
-
Causes of Metabolic Alkalosis
Exogenous HCO3 loads - acute alkali administration
-
Milk alkali syndrome
Effective ECV contraction, Normotension, K depletion and
+
secondary Hyperreninimic Hyperaldosteronism
Renal origin
GI origin Diuretics (thiazide and loop)
Vomiting Edematous states
Gastric aspiration Hypercalcemia - Hypoparathyroidism
Congenital Mg deficiency
+2
chloridorrhea K depletion
+
Villous adenoma Bartter’s syndrome
Gittleman’s syndrome
Recovery from lactic acidosis or
ketoacidosis
Penicillin or Carbenicillin (Non-
reabsorbable anions)
Causes of Metabolic Alkalosis
ECV expansion, Hypertension, K deficiency and Hyperminerocorticoidism
+
High renin level Low renin level
Renal artery stenosis Primary aldosteronism
Accelerated Adrenal adenoma, hyperplasia,
hypertension carcinoma
Renin secretion Cushing’s syndrome or
tumor disease
Ectopic corticotropin
Adrenal enzymatic Adrenal carcinoma
defects
11β - Hydroxylase deficiency Adrenal adenoma
17α - Hydroxylase deficiency Pituitary adenoma
Adrenal adenoma,
hyperplasia, carcinoma Others
Licorice
Smokeless tobaco
Lydia pinkham tablets
Causes of Metabolic Alkalosis
Gain of function mutation of ENAC channel with ECV
expansion, Hypertension, K deficiency and hyporeninimic
+
hyperaldosteronism
Liddle’s syndrome
Consequences of Metabolic Alkalosis
Respiratory
Decreased respiratory drive stimulus ~ Pulmonary
atelectasis
Increased V/Q mismatch d/t impaired hypoxic pulmonary
vasoconstriction
Oxyhb dissociation curve - Left shift
Cardiovascular
Decreased contractility - Decreased Cardiac Output
Arrhythmias
Neurological
Neuromuscular overexcitability
Cerebral vasoconstriction - Decreased cerebral blood flow
Seizures
Metabolic
Hypocalcemia
Hypokalemia
Compensation of Metabolic Alkalosis
Mainly occurs in Lungs - To retain CO2 -
Hypoventilation
Increased carbonic acid
Increased pH
Renal compensation - increased excretion of
HCO3 -
Diagnostic approach
History:
Examination:
Investigations:
Diagnostic approach
Three steps
Step 1: Detection of metabolic alkalosis based on
elevated total venous CO2
Step 2: Evaluation of secondary response -
Hypoventilation (arterial pH and) PaCO2)
Step 3: Determination of cause
Diagnostic approach
Step 2: Evaluation of secondary response
Deviation in PaCO2 from expected value - presence of
complicated respiratory acid - base disorder
Anion gap - >20 mmol/l - superimposed Metabolic
acidosis
Diagnostic approach
Step 4: Determine the cause
BP
Urine electrolytes
Plasma renin
Plasma cortisol
Diagnostic approach
Urine Cl- Chloride unresponsive alkalosis
<20
mEq/L >20
mEq/L
Chloride responsive alkalosis Urine K+
<30 mEq/d >30 mEq/d
Gastric fluid loss
Nonreabsorbable anion Laxative abuse Blood pressure
Severe K+ Low/normal
delivery
Diuretics
depletion High
Posthypercapnea Barrter’s syndrome High
Villous adenoma Gitelman’s Plasma renin
Congenital chloridorrhea syndrome
Diuretic abuse
High Low
High unilateral Normal
renal vein renin Plasma cortisol
Primary
Hyperaldosteronis
Yes m
No High B/l adrenal
Renovascular
HTN Malignant or hyperplasia
accelerated Cushing Licorice abuse
JGA tumor syndrome
HTN
Management
Goals of treatment
A. Correcting the underlying stimulus for HCO 3 generation
-
B. Restoring the ability of kidney to excrete the excess
HCO3 -
Management
Metabolic alkalosis d/t NG drainage or vomiting
Administer IV NaCl
Oral or IV KCl
If NG drainage to be continued
Administer drugs to inhibit gastric secretion to
minimise loss of H and Cl
+ -
Discontinue the diuretic
Potassium sparing diuretics to be used (amiloride,
spironolactone, triamterene)
Corticosteroid induced Metabolic alkalosis
Adrenal adenoma - Surgical removal
Primary hyperaldosteronism
Dietary NaCl restriction and K administration
+
Spironolactone or eplerenone
Hereditary forms of mineralocorticoid excess
(Liddle syndrome, 11β - Hydroxylase deficiency)
Amiloride
Barrter’s syndrome and Gitelman’s syndrome
KCl administration
High K diet
+
ACEI or ARB
NSAID
Correction of Mg depletion
++
K sparing diuretics
Metabolic alkalosis in Congestive Heart
Failure
Fluid overload with Preserved Renal function -
Acetazolamide (to reduce HCO3 ) -
Acetazolamide with aggressive K replacement therapy
+
Carbonic anhydrase inhibitors - block H linked Na
+ +
reabsorption - leading to excretion of both Na and
+
HCO3 )-
Acetazolamide - Decreases ECF volume and lowers
serum HCO3 and stimulates K excretion - cause
- +
hypokalemia
Metabolic alkalosis in Renal
Failure
Continuous venovenous hemofilteration
Serum HCO3 can also be lowered by continuous slow,
-
low-efficiency dialysis, with dialysate HCO3 adjusted to
-
23 mmol/l
Standard hemodialysis and Peritoneal dialysis - Less
useful
