Brief introduction of metabolic alkalosis, causes, investigations and management.

2. METABOLIC ALKALOSIS
Dr. Muhammad Usama Azhar
PGR Medicine

3. Objectives
• Definition
• Classification
• Causes
• Compensatory Mechanism
• Clinical Presentation
• History and Examination
• Investigations
• Management

4. Definition
• Metabolic alkalosis is a primary acid–base disturbance
due to either loss of acid (H) or gain of HCO3 in the ECF.
• The blood has a pH of >7.4 and plasma HCO of >26–28
mEq/L
• The increase in pH that results from the elevation in
(HCO3 − ) induces hypoventilation, producing a
secondary increase in arterial CO2 tension (PaCo2 ).
• Thus, metabolic alkalosis is characterized by coexisting
elevations in serum HCO3 − , arterial pH, and PaCO2.

7. Causes
• Exogenous Administration of Alkali
• ECF contraction (Secondary Hyper-aldosteronism)
• ECF expansion (Primary Hyper-aldosteronism)
• Miscellaneous

8. Exogenous Administration of Alkali
• IV HCO3 overload
• Acute alkali administration
• Milk alkali syndrome

9. ECF contraction (Secondary Hyper-
aldosteronism)
• Gastrointestinal origin
• Vomiting
• Gastric aspiration
• Congenital chloride diarrhoea
• Villous adenoma
• Renal origin
• Diuretcs
• Posthypercapnic stage
• Hypercalcemia/hypoparathyroidism
• Recovery from lactic acidosis or ketoacidosis
• Delivery of nonreabsorbable anions including Penicillin, Carbenicilline
• Hypomagnesemia
• Bartter’s syndrome
• Gitelman’s syndrome

10. ECF expansion (Primary Hyper-
aldosteronism)
• High renin
• Renal artery stenosis
• Accelerated hypertension
• Renin secreting tumor
• Oestrogen therapy
• Low renin
• Primary aldosteronism (adenoma, hyperplasia, carcinoma)
• Adrenal enzyme defects (11 B hydroxylase deficiency, 17 a-
hydroxylase deficiency)
• Cushing’s syndrome or disease

11. Miscellaneous
• Liddle’s syndrome
• Cystic fibrosis
• Ingestion of licorice, carbenolone, chewer’s tobacco
• Hypokalemia
• Hypomagnesemia

12. Causes associated with
contracted ECF volume

13. Vomiting or nasogastric suction
• Results in the loss of hydrochloric acid with the stomach
contents.
• Loss of fluid and NaCl in vomitus results in contraction of
ECF and increased secretion of renin and aldosterone.
• Severe vomiting also causes loss of potassium
(hypokalaemia) and sodium (hyponatremia).
• The kidneys compensate for these losses by retaining
sodium in the collecting ducts at the expense of hydrogen
ions by the action of aldosterone, leading to metabolic
alkalosis.

14. Congenital chloridorrhea
• Rare autosomal recessive disorder which causes severe
diarrhea, fecal acid loss and HCO3 retention.
• The main mechanism is loss of ileal HCO3/Cl anion
exchange mechanism which results in decreased Cl
reabsorption.
• Na+/H+ exchange mechanism remains normal so normal
H+ is secreted in stool which causes Na and HCO3
- to be
retained.
• This results in metabolic alkalosis.

15. Villous adenoma
• High adenoma derived K secretory rate.
• Colonic secretion is alkaline
• K+ and volume depletion most probably causes alkalosis

16. Diuretics
• Loop diuretics and thiazide reduce the ECF without affecting
the total body bicarbonate content.
• Diuretics blocks Na+ and Cl- channels
• More Na+ is delivered to DCT
• Na+ exchange with K+ under the effect of aldosterone
• Kaliuresis and hypokalemia occurs
• Depleted ECF causes contraction alkalosis
• Hypokalemia augments renal ammoniagenesis

17. Post-hypercapnic State
• During respiratory acidosis prolonged CO2 retention
occurs (chronic hypoventilation and hypercapnia)
resulting in increased plasma HCO3
- concentration
• Due to increased reasbsorption and generation of HCO3
-
• When hypercapnia resolves increased HCO3
- content and
associated ECF contraction will cause metabolic alkalosis
• Alkalosis persists until chloride supplementation is given

18. Non-reabsorbable anions
• Administration of large amount of non reabsorbable
anions like penicillin or carbenicillin can enhance distal
acidification and K+ excretion.
• H+ secretion occurs without Cl- dependant HCO3
secretion.
• Mg deficiency also results in hypokalemic alkalosis by
enhancing distal acidification by stimulation of renin and
hence aldosterone secretion.

19. Bartter’s Syndrome
• Autosomal recessive disorder involving impaired Thick
Ascending Limb salt reabsorption.
• Results in salt wasting, volume depletion, and activation
of renin-angiotensin system.
• It is associated with metabolic alkalosis, hypokalemia and
normal to low blood pressure.
• NSAIDs reduce polyuria and salt wasting in Bartter’s
syndrome (increased renal PGE2 production in Bartter’s).

21. Gitelman Syndrome
• Autosomal recessive disorder
• Characterised by metabolic alkalosis, hypokalemia,
hypocalciuria and hypomagnesemia.
• It is caused by loss of function of the thiazide sensitive
sodium-chloride symporter located in the distal convoluted
tubule.

23. Causes associated with
increased ECF volume

24. High Renin
• States with high renin may be accompanied by
hyperaldosteronism and alkalosis.
• Renin levels may be increased due to increased renin
secretion or decreased circulating blood volume.
• Examples of high renin are accelerated hypertension and
renovascular hypertension.
• Estrogen increase renin substrate and hence angiotensin
II formation.
• Primary tumor causing overproduction of renin can also
cause Metabolic alkalosis

25. Low Renin
• I. Hyperaldosternism
• Adenoma, carcinoma and hyperplasia of adrenal gland
results in aldosterone overproduction
• Adrenal enzyme defects (11 B hydroxylase deficiency, 17
ahydroxylase deficiency)
• Aldosterone causes hypokalemia which results in an
increased indirect reabsorption of HCO3 via the rise in
proximal tubular intracellular H+
• Hypokalemia reduces GFR and thereby maintains the
elevated blood HCO3

26. Low Renin
• II. Cushing’s syndrome or disease
• Abnormally high glucocorticoid hormone production
caused by adrenal gland adenoma or carcinoma or
ectopic corticotrophin production can cause metabolic
alkalosis

27. Liddle Syndrome
• Autosomal dominant disorder
• Continuous activation of ENaC in collecting duct leading
to increased Na absorption
• Early and severe hypertension with low renin and
aldosterone
• Hypokalemia and metabolic alkalosis
• Amiloride or triamterene block ENaC (basis of treatment)

29. Hypokalemia & Metabolic Alkalosis
• Hypokalemia results in the shift of hydrogen ions
intracellularly.
• The resulting intracellular acidosis enhances bicarbonate
re-absorption in the collecting duct.

30. Hypokalemia & Metabolic Alkalosis
• Hypokalemia stimulates the apical H+ /K+ ATPase in the
collecting duct

32. Hypokalemia & Metabolic Alkalosis
• Hypokalemia stimulates renal ammonia genesis and
alphaketoglutarate is produced, the metabolism of which
generates bicarbonate that is returned to the systemic
circulation.

34. Hypokalemia & Metabolic Alkalosis
• It leads to impaired chloride ion re-absorption in the distal
nephron. This results in an increase in luminal
electronegativity, with subsequent enhancement of
hydrogen ion secretion

36. Consequences
• Cardiovascular
• Arteriolar vasoconstriction
• Decreased coronary blood flow
• Cecreased myocardial contractility
• Increased risk of arrhythmia
• Respiratory
• Hypoventilation
• Metabolic
• Decreased K+ , Ca+ , Mg + , PO4
• Neurological
• Seizures

37. Compensation
1. Respiratory Compensation
2. Renal Compensation

38. Respiratory Compensation
• Respiratory compensation for metabolic alkalosis is less
predictable than that for metabolic acidosis.
• PaCO2 can be estimated by adding 15 to the HCO3 when
HCO3 range is from 25 to 40 mEq/L
• Further elevation in PaCO2 is limited by hypoxemia and
to some extent hypokalemia, which normally
accompanies metabolic alkalosis.
• PaCO2 usually does not increase beyond 55mmHg,
because further bradypnea will cause hypoxemia.

39. Respiratory Compensation
• Compensation for metabolic alkalosis occurs mainly in the
lungs, which retain carbon dioxide (CO2 ) through
hypoventilation.
• CO2 is then consumed toward the formation of the
carbonic acid, thus decreasing pH.
• The decrease in H+ suppresses the peripheral
chemoreceptors, which are sensitive to pH.
• But, because respiration slows, there's an increase in
PCO2 which offsets the depression because of the action
of the central chemoreceptors which are sensitive to the
partial pressure of CO2 in the cerebral spinal fluid. So,
because of the central chemoreceptors, respiration rate
would be increased.

40. Renal Compensation
• Renal compensation for metabolic alkalosis consists of
increased excretion of HCO3 –
• Filtered load of HCO3 - exceeds the ability of the renal
tubule to reabsorb it.
• The development of metabolic alkalosis hence means the
failure of kidneys to eliminate HCO3 at normal capacity

41. Clinical Presentation
• Symptom of metabolic alkalosis are not specific.
• It depends on etiology and severity of disease.
• Include changes in central and peripheral nervous system
function
• Hypoventilation develops because of inhibition of the
respiratory center in the medulla.

42. Clinical Presentation
• Mental confusion, obtundation, predisposition to seizure is
common.
• Aggravation of arrhythmia and hypoxemia in COPD may
also be seen.
• Symptoms of hypokalemia like muscle cramps, myalgia
and muscle weakness may also be seen.
• Symptoms of hypocalcemia (eg, jitteriness, perioral
tingling, muscle spasms) may be present.

44. Background History
• History of congential adrenal hypoplasia
• History of cystic fibrosis
• History of CCF (suggesting chronic exposure to diuretics)
• History of uncontrolled hypertension (malignant
hypertension or renal artery stenosis)
• Deafness , Recurrent dehydration (bartter syndrome)
• Hypertension (hypermineralocorticoid state)

45. Recent History
• Recent antacid consumption
• Recent use of calcium supplements
• β-lactam antibiotic use
• Massive abuse of licorice
• History of diarrhoea (villous adenoma) or vomiting
(chloride loss)
• History of recent hypercapneic respiratory failure
• Intake of sodabicarbonate
• Massive blood transfusion, (citrate bicarbonate)
• Total parenteral nutrition (TPN) ( acetate bicarbonate)

46. Examination
• Clinically, findings consistent with severe hypertension
(eg. retinal changes)
• Renal artery stenosis bruit
• Peripheral oedema (suggesting chronic exposure to
diuretics)

47. ABGs in Metabolic Alkalosis
• Arterial pH increased (> 7.45)
• Serum bicarbonate increased (> 26meq/l)
• PaCO2 increased
• PaCO2 rises 7 mmHg per 10 meq/L bicarbonate rise
• The anion gap is frequently elevated to a modest degree
in metabolic alkalosis because of the increase in the
negative charge of albumin and the enhanced production
of lactate.

48. ABGs in Metabolic Alkalosis
• Normally, arterial PaCO2 increases by 0.5-0.7 mm Hg for
every 1 mEq/L increase in plasma bicarbonate
concentration.
• If the change in PaCO2 is not within this range, then a
mixed acid-base disturbance occurs.
• If the increase in PaCO2 is more than 0.7 times the
increase in bicarbonate, then metabolic alkalosis coexists
with primary respiratory acidosis.
• If the increase in PaCO2 is less than the expected
change, then a primary respiratory alkalosis is also
present.

49. Approach to Metabolic Alkalosis

50. Approach to Metabolic Alkalosis

51. Investigations
• Urinary chloride
• ↑Renin & ↑ aldosterone → Renovascular hypertension
Renin secreting tumor
• ↓Renin & ↑ aldosterone → Adrenal adenoma
Glucocorticoid usage
• ↓Renin & ↓aldosterone → Cushing & Liddle syndrome
Licorice
• Elevated 24 hour urinary cortisol → Cushing syndrome
• Elevated 11 de-oxycortisol → 17 alpha hydro.deficiency,
11 beta hydro.deficiency

52. Management
• Chloride-Responsive Metabolic Alkalosis
• Re-expand volume with normal saline (primary therapy)
• Supplement with Potassium to treat hypokalemia
(alkalosis associated with severe hypokalemia will be
resistant to volume resuscitation until K+ is repleted)
• H+ blockers or PPIs if vomiting/NG suction to prevent
further losses in H+ ions

53. Management
• Chloride-Responsive Metabolic Alkalosis
• Discontinue diuretics
• Acetazolamide if normal saline is contraindicated due to
CHF. (Monitor for hypokalemia)
• NH4Cl ( 100 meq/L per 20 mL vial) 1-2 vials in 1000 mL of
normal saline.
• Hemodialysis in patients with marked renal failure

54. Management
• Chloride–Unresponsive Metabolic Alkalosis
• Surgical removal of mineralocorticoid producing tumor
• Aldosterone inhibitors
• ACE inhibitors
• Discontinue corticosteroids
• Potassium repletion (only intervention needed to treat the
alkalosis)