Metabolic Alkalosis

Mazen Kherallah, MD, FCCP, FCCM, FACP

Michigan State University

Society of Critical Care Medicine

Metabolic AlkalosisDefinition

• Elevated HCO3-

• Decline in [H+] in the ECF

Metabolic Alkalosis

HCO3/ECF Volume

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:– Bartter’s-like syndromes– Current diuretic use

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

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

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+

Addition of HCO3- to the ECF

Loss of Cl- AnionGain of HCO3

- in Plasma

Vomiting or nasogastric suction Cl- loss in urine

Addition of HCO3- to the ECF

Retention of NaHCO3

Gain 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

Mechanisms for Renal Retention of HCO3

-

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

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

Causes Associated with ECF Volume Contraction

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

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

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

Ammoniagenesis

AmmoniagenesisWhen K is high in the lumen, fewer NH4 is reabsorbed because of thecompetition between NH4 and K.With hypokalemia more NH4 is reabsorbed and then secreted as NH3 combining with H and raising the HCO3 in plasma

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

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

3. Nonreabsorbable Anions

• Cl in urine should be < 20

• Na in the urine should be high

• Na + K should be > Cl due to the presence of unmeasured anion

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

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

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

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

Causes Associated with Normal or Expanded ECF Volume

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

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

3. Magnesium Depletion

• Mg enhances the NKCC mechanism

• Depleted Mg results in higher Na and Cl excretion and Hypokalemia with metabolic alkalosis

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

A lka li in takeIon -exch an g e res in sm ilk a lka li s yn d rom e

V om itin g

Y es

D iu re ticsB artte r

M g d ep le tion

> 2 0

L oss o f g as tricflu id

D iu re ticR are cau ses

< 1 0

Y es

E xog en ou sm in era lcortico id s

C u sh in g 's syn d rom e

B oth low

P rim aryh yp era ld os te ron ism

L ow ren inH ih g a ld o

R A SR en in tu m or

M alig n an t h yp erten s ion

B oth h ig h

W ah t is th eren in an da ld o leve l

N o

Is E C F vo lu m econ trac ted

N o

Is G F R very low

M etab o lic A lka los is

Urine Cl

Reabsorption of Na+ in CCD

Na

K

Na

K

Na

K

Na-K ATPase

Na

K

Na Cl Cl Na

Cl K

Cl K

ElectrogenicElectroneutral

ClCCD

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.

Plasma Urine

Na 133 52

K 3.1 50

Cl 90 0

HCO3 32 -

pH 7.48 8

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?

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

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

Plasma Urine

Na 138 63

K 2.7 34

Cl 96 0

HCO3 30 0

pH 7.45 5.6

Creatinine 0.7 -

Osmolality 287 563

A lka li in takeIon -exch an g e res in sm ilk a lka li s yn d rom e

V om itin g

Y es

D iu re ticsB artte r

M g d ep le tion

> 2 0

L oss o f g as tricflu id

D iu re ticR are cau ses

< 1 0

Y es

E xog en ou sm in era lcortico id s

C u sh in g 's syn d rom e

B oth low

P rim aryh yp era ld os te ron ism

L ow ren inH ih g a ld o

R A SR en in tu m or

M alig n an t h yp erten s ion

B oth h ig h

W ah t is th eren in an da ld o leve l

N o

Is E C F vo lu m econ trac ted

N o

Is G F R very low

M etab o lic A lka los is

Urine Cl

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

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

Plasma Admission 4 hours later

pH Not done 7.50

PaCO2 Not done 48

HCO3 62 48

K 3.1 4.0

Anion gap 15 13

Creatinine 2.3

Urinevolume

60 ml

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

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.

Plasma

Na 130 H 30

K 2.9 pH 7.53

Cl 80 PaCO2 25

HCO3 20 PaO2 60

Creatinine 1.4 Albumin 38

Urea 12 Glucose 150

Osmolality 320 Ketones Weakly +

Expected Responses to Primary Acid-Base Disorders:

Disorder ResponseMetabolic acidosis Drop the 7 and the decimal point from the pH

For every mmol/L fall in HCO3 from 25, Paco2 drops 1mm Hg

Metabolic alkalosis Drop the 7 and the decimal point from the pHFor every mmol/L rise in HCO3 from 25, Paco2 shouldrise 0.7 mm Hg

Acute respiratoryacidosis

For every twofold increase in Paco2, the plasma HCO3should increase by 2.5 mmol/L from 25

Chronic respiratoryacidosis

For every mm Hg increase in Paco2, the plasma HCO3should increase by 0.3 mmol/L from 25

Acute respiratoryalkalosis

For every mm Hg fall in Paco2, the plasma H+ should fallby 0.8 mmol/L from 40

Chronic respiratoryalkalosis

For every mm Hg in Paco2, the plasma HCO3 should fallby 0.5 mmol/L from 25

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

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

Plasma Urine

Na 107 3

K 1.9 12

Cl 67 7

HCO3 30 0

pH 7.47 5.1

Urea 4.2 -

Glucose 108 0

Osmolality 220 405

Is This Bartter’s 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

Plasma(admission)

Plasma(day 14)

Urine

Na 140 140 49

K 3.8 1.6 36

Cl 105 91 82HCO3 26 38 0

pH 7.40 7.48 5.5

Creatinine 0.7 0.6 -

BUN 11 10 -

Mg 2.2 2.2 -

Volume - - 3

Na+

2Cl-

K+

Na+ K+

Na+ K +

Na+

Ca++

Mg++

Cl-K+

Driven by lumen positive charges

ATP

2 Na+

2 Cl-

H2O

H2O

Ca receptorsalso binds cations likegentamicin

NKCC

ROM K-1

Case # 7

• Alicia is a 47 year old with history of Hypertension which is controlled with diuretics.

• Presented with dizziness and contracted ECF

Plasma Urine

Na 138 36

K 2.7 61

Cl 99 57

HCO3 28 0

pH 7.46 5.9

Mg 1.0 4

Creatinine 1 -

Osmolality 287 563