Metabolic Alkalosis

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Metabolic Alkalosis

• Mazen Kherallah, MD, FCCP, FCCM, FACP
• Michigan State University
• Society of Critical Care Medicine

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Metabolic AlkalosisDefinition

• Elevated HCO3-
• Decline in H in the ECF

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Metabolic Alkalosis
?HCO3/?ECF Volume
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Causes of Metabolic AlkalosisCauses associated
with contracted ECF volume

• Low urine Cl
• Loss of gastric secretions vomiting, nasogastric
  suction
• Remote use of diuretics
• Delivery of nonreabsorbable anion plus Na
  Carbenicilline
• Posthypercapnia
• Loss NaCl in GI congenital Cl loss, villous
  adenoma
• Persistent high urine Cl
• Bartters-like syndromes
• Current diuretic use

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Causes of Metabolic AlkalosisCauses associated
with normal or expanded ECF volume

• Large reduction in GFR plus a source of HCO3
• Alkali ingestion
• Enhanced mineralocorticoid activity
• primary aldosteronism
• Secondary hyperaldosteronism renal artery
  stenosis, malignant hypertension, renin producing
  tumor, low effective arterial blood volume with
  an alkali load
• Endogenous or exogenous mineralocorticoid,
  licorice ingestion, ACTH secretion

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Metabolic Alkalosis

• Extracellular elevation of HCO3-
• Absolute by addition of HCO3- to the ECF
• Relative by the loss of ECF volume
• Intracellular events
• Hypokalemia Kaliuresis
• Intracellular acidosis replacement of K by H

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Addition of HCO3- to the ECF

• With the constraints of electroneutrality, there
  are only two ways to add a specific anion HCO3-
  to a compartment
• Loss of an anion such as Cl-
• Retention of a cation such as Na

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Addition of HCO3- to the ECF Loss of Cl-
AnionGain of HCO3- in Plasma
Vomiting or nasogastric suction
Cl- loss in urine
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Addition of HCO3- to the ECF Retention of
NaHCO3Gain of HCO3- in Plasma

• When Na is retained in the ECF, its volume is
  expanded
• If GFR is normal this extra Na and bicarbonate
  will be excreted via the kidney
• GFR should be low (permission of the kidneys) to
  retain extra Na and HCO3

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Mechanisms for Renal Retention of HCO3-
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Contraction of the ECF VolumeIncreased HCO3-

• The ECF volume is contracted secondary to removal
  of NaCl and water
• The HCO3- is increased and the content is
  unchanged
• Same HCO3- are distributed in smaller volume
• Metabolic alkalosis contraction alkalosis

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Contraction of the ECF VolumeDiuretic Ingestion

• Diuretic ingestion causes NaCl loss in the urine
  and ECF volume contraction
• Increased production and excretion of NH4
  consequent to hypokalemia, thus new HCO3
  formation

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Causes Associated with ECF Volume Contraction

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1. Vomiting or Nasogastric Suction

• Loss of HCl
• Generation of HCO3
• Excretion of NaHCO3 in the urine
• ECF contraction
• Renin will increase angiotensin II and
  aldosterone
• Excretion of K kaliuresis

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How many liters of emesis must be lost in order
to raise the HCO3- in plasma by 10 mmol/L in
70-kg adult?

• Extracellular HCO3- is 25 mmol/L and
  intracellular is 10 mmol/L
• 10 X 15 150 mmol extracellular
• 3.5 X 30 100 mmol intracellular
• Total HCO3 added is 250
• 1 liter of gastric fluid contains 100 mmol of H
  and 100 mmol of Cl-
• 2.5 liters is needed to be lost before HCO3 is
  raised to 35

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2. Diuretics

• Diuretics blocks Na and Cl channels
• More Na is delivered to DCT
• Na exchange with K under the effect of
  aldosterone
• Kaliuresis and hypokalemia ensues
• Depleted ECF and high aldosterone leads to
  hypokalemia
• Hypokalemia augments renal ammoniagenesis

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Ammoniagenesis
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Ammoniagenesis
When K is high in the lumen, fewer NH4 is
reabsorbed because of the competition between NH4
and K. With hypokalemia more NH4 is reabsorbed
and then secreted as NH3 combining with H and
raising the HCO3 in plasma
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Intracellular Acidosis in Metabolic Alkalosis
associated with Hypokalemia

• The depletion of K leads to a shift of cation Na
  and H into the cells
• This shift exacerbates the degree of HCO3
  elevation in the ECF and cause intracellular
  acidosis
• Hypokalemia must be corrected first

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3. Nonreabsorbable Anions

• If a patient has a contracted ECF volume and
  takes an Na salt with an anion that cannot be
  reabsorbed by the kidney Carbenicillin
• There is stimulus for Na reabsorption but it
  cannot be reabsorbed.
• In CCD the action of aldosterone will lead to
  hypokalemia
• Hypokalemia will cause more ammoniagenesis and
  thus increased plasma HCO3 and metabolic
  alkalosis

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3. Nonreabsorbable Anions

• Cl in urine should be lt 20
• Na in the urine should be high
• Na K should be gt Cl due to the presence of
  unmeasured anion

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4. Posthypercapnia

• During chronic hypoventilation and hypercapnia,
  plasma HCO3 concentration is increased.
• HCO3 is generated in the kidney and excretion of
  NH4Cl ensues
• When hypercapnia resolves increased HCO3 content
  will cause metabolic alkalosis

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5. Loss of NaCl via the GI tract

• Congenital chloridorrhea, villous adenoma
• Loss of Na and Cl in stool
• Similar to diuretic induced metabolic alkalosis
• The urine always has Na and Cl

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6. Bartter-like Syndromes

• Hypokalemia
• Renal Na and Cl wasting
• Contracted ECF volume
• Metabolic alkalosis
• hypereninemia
• Deficiency of Mg
• Hypertrophy of justaglomerular apparatus
• High rate of Ca excretion

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6. Bartter-like Syndromes

• The pathophysiology can be considered as having a
  loop diuretic acting 24 hour a day
• Defect in Na, K, 2 Cl electroneutral
  cotransporter NKCC in the Luminal membrane of
  the thick ascending limb of Henle
• this causes delivery of Na and Cl to CCD and thus
  K excretion
• NaCl wasting and a low ECF volume results in high
  level of renin

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Causes Associated with Normal or Expanded ECF
Volume

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1. Hyperaldosteronism

• Aldosterone causes hypokalemia
• Hypokalemia enhances ammoniagenesis, which
  enables renal new CO3 formation
• Hypokalemia causes an increased indirect
  reabsorption of HCO3 via the rise in proximal
  tubular intracellular H
• Hypokalemia reduces GFR and thereby maintains the
  elevated blood HCO3

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2. Alkali Loading

• Under usual circumstances, NaHCO3 loading leads
  to only a mild elevation in plasma HCO3 because
  most of these HCO3 are excreted
• In the presence of Na depletion or in renal
  failure, clinically important elevation of plasma
  HCO3 occur with NaHCO3 administration

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3. Magnesium Depletion

• Mg enhances the NKCC mechanism
• Depleted Mg results in higher Na and Cl excretion
  and Hypokalemia with metabolic alkalosis

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4. Milk-Alkali Syndrome

• Ingestion of large amount of milk and absorbable
  antacids CaCO3
• Patient excrete large amount of Ca and HCO3 in
  the urine
• Ca deposits more in alkaline urine
• Deposition of Ca leads to renal function
  impairment
• Thus HCO3 increased in plasma

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Urine Cl
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Reabsorption of Na in CCD
Electroneutral
Electrogenic
Na K
Na K
Na K
Na Cl
Cl Na Cl K Cl K
Na K
Na-K ATPase
CCD
Cl
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Case 1

• Toby, a 26-year old dancer, complains of
  weakness. She denies vomiting and the intake of
  medications other than vitamins.
• Physical examination reveals a thin woman who has
  a contracted ECF volume.

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Questions????

• What acid-base disturbance is present?
• Why is the Na in urine not lower, given the
  presence of ECF volume contraction?
• Why is Toby hypokalemic?
• What is the basis for the acid-base disturbance?

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Discussion of Case 1

• Metabolic alkalosis with hypokalemia
• Cl is low in urine because of the ECF volume
  contraction and reabsorption of NaCl
• Na is high in the urine because it is excreted
  with an anion other than Cl
• The very high urine pH indicated that the other
  anion is HCO3 bicarbonaturia
• To the degree that the filtered load of HCO3
  exceeds the tubular capacity to reabsorb it, HCO3
  are excreted
• Hypokalemia secondary to high urine delivery to
  CCD and high aldosterone secondary to contracted
  ECF volume
• Body shape disorder and induced vomiting

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Case 2

• Farrah, a beautiful person, is concerned about
  her body image so she diets most of the time. Her
  food intake is erratic and consists mainly of
  vegetables and fruits she consumes little meat
  or table salt. She jogs 60 Km per week and is
  asymptomatic.
• When she volunteered for a clinical research
  project, she was surprised to find that she was
  hypokalemic. She denied vomiting and the use of
  diuretics or laxatives. Her ECF is contracted

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Urine Cl
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Discussion of case 2

• ECF volume contraction, metabolic alkalosis with
  hypokalemia and high aldosterone level
• ECF volume contraction with 0 Cl in urine but
  high Na
• Positive urine net charge indicative of an anion
  other than Cl is present
• Low pH and high osmolal gap indicates that the
  anion is not HCO3 (bicarbonate is 0)
• Negative NaCl balance because of poor dietary
  intake and nonrenal loss, she has an unusual
  organic anion load from her diet

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Case 3

• Solly has episodes of abdominal pain and profuse
  diarrhea for months. More recently he has vomited
  on occasion and has suffered from episodic
  tingling and weakness. He took antacids to
  relieve his abdominal pain, but their beneficial
  effect was transitory.
• Each time his condition reverts to normal without
  therapy

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Discussion of Case 3

• Metabolic alkalosis with hypokalemia
• Bicarbonate gain of non-renal cause secondary to
  gastric HCl secretion
• Most-likely HCl loss from GI
• Low rate of excretion of HCO3 due to decreased
  GFR
• ECF volume is not contracted due to Low GFR
• HCl reabsorption led to improvement in metabolic
  alkalosis
• Zollinger-Ellison syndrome

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Case 4

• Mr. Green is 42 year old and is a chronic
  alcoholic. He was brought to the emergency room,
  obviously intoxicated. He had been lying in the
  park in a pool of vomitus. On physical
  examination, he was unkempt and incoherent. He
  had a markedly contracted ECF volume, was febrile
  (39) and had evidence of pneumonia.

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Expected Responses to Primary Acid-Base Disorders
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Discussion of Case 4

• Metabolic acidosis with increased anion gap most
  likely alcoholic ketoacidosis, and L-lactic
  acidosis type B secondary to thiamin deficiency
• Metabolic alkalosis with vomiting and hypokalemia
• Respiratory alkalosis from pneumonia

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Case 5

• Emily is 73 year old, she enjoys toast with jam
  along with her traditional cup of tea.
• On her annual checkup, her physician told her
  that her blood pressure is elevated 170/95, and
  gave her thiazide diuretic.
• She has not been feeling well since she took her
  medicine, she feels weak, she becomes lightheaded
  when she stands up, and she is less able to
  perform at her high intellectual level, she
  drinks a lot of water
• On P.E. blood pressure 150/90 and orthostatic of
  15 mm Hg, her urine volume is 0.5 L per day

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Is This Bartters Syndrome

• 50 year old paraplegic male has a neurogenic
  bladder as a result of MVA. He developed a UTI
  and was treated with gentamicin 80 mg q8h for 2
  weeks.
• There was no special findings on physical
  examination, his ECF is not low
• Hypokalemia did not improve with 200 mmol per
  day. Urine output 2-5 L per day

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Driven by lumen positive charges
H2O
Na K
Na Ca Mg
Na K
NKCC
ATP
Na 2Cl- K
Ca receptors also binds cations like gentamicin
ROM K-1
Cl-
K
2 Na 2 Cl- H2O
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Case 7

• Alicia is a 47 year old with history of
  Hypertension which is controlled with diuretics.
• Presented with dizziness and contracted ECF

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