Download Metabolic Alkalosis

pathophysiology

Alkalemia: (↑ arterial pH) + ↑ in plasma
bicarbonate.
pathophysiology

 evaluation of patients with metabolic alkalosis must
consider two separate issues :
 (1) initial process that generates metabolic alkalosis.
 (2) alterations in renal function that maintain
alkalemic state.
Generation of metabolic alkalosish

 Can result from excessive losses of H+ ion from kidneys
or stomach or gain secondary to ingestion or
administration of bicarbonate-rich fluids.
 With vomiting & nasogastric suctioning, H+ ion is lost
externally & metabolic alkalosis results.
 Secretory diarrheas often result in excessive GI losses of
chloride-rich, bicarbonate-poor fluid .
 Bicarbonate administration or infusion of organic
anions that are metabolized to bicarbonate (acetate,
lactate, citrate) .
Generation of metabolic alkalosish

 Diuretic agents acting on thick ascending limb of
loop of Henle (furosemide) & distal convoluted
tubule (thiazides) promote excretion of Na+ & K+
almost exclusively in association with Cl-, without
proportionate ↑ in bicarbonate excretion.
 Renal ammoniagenesis can also be stimulated by
concomitant hypokalemia →↑ net acid excretion.
Generation of metabolic alkalosish

 ↑ mineralocorticoid activity resulting from Cushing's
syndrome, primary hyperaldosteronism, or
hyperaldosteronism secondary to ↑ renin activity (in case of
malignant hypertension).
 →stimulate collecting duct H+ ion secretion & indirectly ↑
ammoniagenesis by causing hypokalemia
 High doses of penicillins (e.g., ticarcillin) can produce
metabolic alkalosis (because they act as nonreabsorbable
anions ).
Maintenance of metabolic alkalosis:

 Maintenance of metabolic alkalosis:
 1.volume-mediated processes (NaCl –responsive)
 2.volume-independent processes (NaCl –resistant)
that are predominantly associated with excess
mineralocorticoid activity & hypokalemia
Maintenance of metabolic alkalosis:

 Intravascular volume depletion: ↓ GFR ↓ filtered load of
bicarbonate →↓ kidney's ability to excrete bicarbonate load.
 important in CKD & patients with intravascular volume
contraction.
 ↓ effective arterial blood volume also ↑ proximal & distal
tubular Na+ reabsorption [must be coupled with
reabsorption of anion (Cl- or bicarbonate), or exchange with
cation (K+ or H+) to maintain charge neutrality].
In proximal tubule, ↑Na+ reabsorption stimulates
bicarbonate reabsorption.
In distal nephron, ↑Na+ reabsorption, particularly in
hypokalemia, stimulates H+ ion secretion.
Maintenance of metabolic alkalosis:

 persistent hypokalemia leads to:
1- ↑proximal tubular bicarbonate reabsorption
2- stimulating ammoniagenesis
3- ↑ distal tubular H+ ion secretion
 Mineralocorticoid excess stimulates collecting duct H+
ion secretion.

Causes of Metabolic Alkalosis
Differentiated by Responsiveness
to NaCl

 NaCL–responsive (urinary Cl- concentration <10
mEq/L):
 GI disorders
- Vomiting
- Gastric drainage
- Chloride diarrhea
 Diuretic therapy
 Correction of chronic hypercapnia
 Cystic fibrosis
 Excessive bicarbonate therapy of organic acidosis
 hypokalemia

 NaCl–resistant (urinary Cl- concentration >20
mEq/L) :
 Excess mineralocorticoid activity :
- Hyperaldosteronism
- Cushing's syndrome
 Excessive black licorice intake
 Profound potassium depletion
 Magnesium deficiency
 Estrogen therapy

 Unclassified
 Alkali administration
 Milk-alkali syndrome (Homework)
 Massive blood or plasma protein fraction transfusion
 Nonparathyroid hypercalcemia
 Carbohydrate refeeding after starvation
 Large doses of penicillin
Clinical Presentation

 Mild to moderate metabolic alkalosis: symptoms
related to underlying cause ( muscle weakness with
hypokalemia or postural dizziness with volume
depletion).
 Severe alkalemia (blood pH >7.60) → cardiac
arrhythmias, particularly in patients with heart
disease, hyperventilation, & hypoxemia.
 Neuromuscular irritability can be present, with signs
of tetany or hyperactive reflexes; possibly due to ↓
ionized Ca concentration (↓competition from H+ ions
for binding sites on albumin molecule).
 Mental confusion, muscle cramping & paresthesia can
also occur.
Compensation

Respiratory response to metabolic alkalosis is
hypoventilation →↑ PaCO2 - initiated within
hours when central & peripheral
chemoreceptors sense ↑ pH.
compensation

 PaCO2 ↑ 6-7 mm Hg for each 10 mEq/L ↑ bicarbonate,
up to PaCO2 of ~50-60 mm Hg before hypoxia sensors
react.
 If PaCO2 is normal or < than normal, one should
consider superimposed respiratory alkalosis, which
can be secondary to fever, gram-negative sepsis, or
pain.
compensation

 Limitations: respiratory compensation
(hypoventilation →↑ PCO2) →↑ renal acid secretion
& ↑serum HCO3 concentration similar to that
induced by primary respiratory acidosis →will
decrease the pH benefit of hypoventilation.
 This effect could raise arterial pH to value higher
than that which would have occurred in the absence
of respiratory compensation.
THE CASE
“I can’t stop throwing up.”
HPI

 Henry Greene is a 43-year-old African-American
man who presents to the ED with complaints of
uncontrolled vomiting, fatigue, generalized
weakness, and myalgias over the past 24 hours. He
also reports a fever of 102°F (38.9°C) from this
morning.
PMH

 Hypertension × 20 years
 Hyperlipidemia
 Chronic kidney disease (SCr 2.2 mg/dL 1 year ago);
has never been on dialysis
FH

 Father is alive with a history of HTN, CAD, and MI.
Mother is deceased × 3 years. She had a history of
breast cancer and type 1 diabetes mellitus. Brother is
alive with HTN.
SH

 “Social” alcohol use reported. Further questioning
reveals consumption of four to six beers on weekend
days. There is no history of tobacco or illicit drug use
reported. He is a computer software engineer and
lives at home with his wife and two children. He has
not seen a doctor in almost one year.
ROS

 The patient denies recent weight gain or loss, but
he reports a 24- hour history of fever, chills, sore
throat, cough, N/V, nasal congestion, and severe
headache. He also reports uncharacteristic
fatigue and weakness. No reported chest pain,
palpitations, or diaphoresis. He denies diarrhea,
constipation, or change in bowel habits or color
of stool. Urine output has decreased over the
past 24 hours since he reports last taking his
medication or anything else by mouth. He
reports increased thirst.
Meds

 Furosemide 40 mg po daily
 Lisinopril 20 mg po daily
 Calcium carbonate 500 mg po TID with meals
 Atorvastatin 20 mg po daily
 All
 PCN—hives (cephalexin used in the past with no
allergic reaction)
Physical Examination

 Gen
The patient is ill-appearing and feels warm to the touch
 VS
BP 155/89, HR 82, RR 19, T 39.8°C; Wt 80 kg, Ht 5'9''; O2 sat 97%
on RA
 Skin
Soft, intact, warm, dry
 HEENT
EOMI; PERRLA; sclerae anicteric; funduscopic exam shows AV
nicking; no sinus tenderness; dry mucous membranes; no oral
lesions; nasal congestion present
Physical Examination

 Neck/Lymph Nodes
No JVD or bruits; no lymphadenopathy or thyromegaly
 Chest
Lungs CTA bilaterally
 CV
RRR; normal S1, S2, no S3, or S4; no murmurs, rubs, gallops
 Abd
Soft, NTND; (+) bowel sounds
 GU
Noncontributory
Physical Examination

 Ext
Distal pulses 2+ bilaterally; femoral pulses 2+
bilaterally
 Neuro
A & O × 3. UE strength 3/5, LE strength 3/5. CNs II–
XII intact.
Babinski negative bilaterally.
Labs


 ABG
pH 7.51, pCO2 48 mm Hg, pO2 85 mm Hg on RA
 UA
Urine sodium 13 mEq/L; potassium 10 mEq/L;
chloride 9 mEq/L
 Chest X-Ray
Unremarkable
 ECG
Normal
Assessment

 Admit patient for flu-like symptoms, acute-onchronic kidney disease, electrolyte abnormalities,
and metabolic alkalosis.
Problem Identification

 1.a. Identify the type of acid–base disturbance
present in this patient. Explain how the patient’s
arterial blood gas results and medical history
support your response.
 Blood PH 7.51 which represent alkalemia.
 PCO2 48mmHg which is high.
 Serum HCO3 37.01 mEq/L which is high.
 Patient is in compensated metabolic alkalosis.
Problem Identification

 Serum [HCO3] Calculation :
PH= 6.1 + log ([HCO3-]/(PCO2*0.03))
7.51= 6.1 + log ([HCO3-]/(48*0.03))
1.41= log ([HCO3-]/1.44)
[HCO3]= 37.01 mEq/L
 Vomiting and the use of loop diuretic can cause
metabolic alkalosis.
Problem Identification

 1.b. Create a list of this patient’s drug therapy
problems.
 Metabolic alkalosis secondary to loop diuretic use
and vomiting.
 (generalized weakness, fatigue,myalgias) likely the
result of volume depletion.
 Electrolyte abnormalities, including: hypokalemia,
hypochloremia and elevated serum bicarbonate.
 AKI
Problem Identification

 1.c. Describe the clinical findings that are consistent
with metabolic alkalosis and those that are inconsistent
with this acid–base disorder.
 Findings that can be seen such as weakness, fatigue, and
myalgias are due to the volume depletion and electrolyte
abnormalities that occur because of alkalosis; they are not
directly due to the alkalosis.
 Consistent findings (laboratory):
 Elevated arterial blood pH
 Elevated serum bicarbonate
 Decreased serum chloride
Problem Identification

 Decreased serum potassium
 Urine chloride <10 mEq/L
 Elevated urine potassium
 Elevated urine pH
Problem Identification

 1.d. Explain how severe vomiting can result in
metabolic alkalosis.
 Vomiting of gastric contents, which are abundant in
hydrochloric acid (HCl), will cause an increase in
serum bicarbonate.
 the rapid loss of chloride anions with hydrogen
causes an abrupt increase in serum bicarbonate
producing a metabolic alkalosis, Although
compensation can occur through the renal excretion
of bicarbonate
Problem Identification

 1.e. Explain how diuretics such as furosemide can
result in metabolic alkalosis.
 The use of loop diuretic (furosemide) causes an
inhibition of ion reabsorption (Na,Cl,K,H) through
the loop of Henle. This leads to increased excretion
of (Na,K,Cl,H and water)
Desired Outcome

 2. What are the desired therapeutic outcomes for this
patient?
 Normalize blood pressure (goal less than 130/80 mm Hg).
 Achieve urine output 0.5 mL/kg/h or more.
 Cessation of vomiting
 Correction of pH to 7.35–7.45
 Correction of serum bicarbonate to 22–30 mEq/L
 Correction of serum chloride to 95–105 mEq/L
 Correction of serum potassium to 3.5–5.0 mEq/L
Desired Outcome

 Correction of urine pH to less than 6.0
 Correction of volume depletion
 Prevention/minimization of complications
 Normalization of body temperature
 Resolution of weakness, fatigue, and myalgias
Therapeutic Alternatives

 3. What pharmacologic and nonpharmacologic
alternatives should be considered for the treatment
of metabolic alkalosis in this patient?
Therapeutic Alternatives

 IV fluid resuscitation with isotonic sodium chloride
is first line therapy in chloride-responsive cases
(urine chloride <10mEq/L). Isotonic sodium chloride
will restore extracellular fluid volume and in
patients with normal renal function, bicarbonate
excretion will be enhanced as sodium, potassium,
and chloride stores are repleted.
 Fluid therapy should be cautiously administered or
not given in patients who are volume overloaded or
who may have difficulty with excess volume
(patients with renal insufficiency).
Therapeutic Alternatives

 Although this patient has renal insufficiency it is
obvious based on presentation that he is severely
volume depleted; therefore, cautious administration
of isotonic sodium chloride should be initiated.
 Potassium supplementation is usually needed
because metabolic alkalosis resulting from diuretic
therapy and/or vomiting causes potassium
depletion. Caution should be given when potassium
supplementation is initiated in patients with renal
insufficiency.
Therapeutic Alternatives

 Acetazolamide is an alternative for patients who are
unable to tolerate increased fluid volume. acetazolamide
stimulates the excretion of potassium and phosphate. It is
not recommended if the patient is experiencing
hypokalemia, but if it is used in this situation, potassium
supplementation should be initiated.
 Acidifying agents (i.e., ammonium chloride, arginine
monohydrochloride,HCl) may be considered in patients
with severe (pH >7.55) symptomatic metabolic alkalosis,
as well as patients who are not responsive to sodium
chloride hydration therapy and those who are not able to
endure excessive volume replacements due to edematous
states.
Therapeutic Alternatives

 Hemodialysis may be considered in patients with
advanced renal failure, who are volume overloaded
and resistant to acetazolamide. With hemodialysis,
the use of either a low-bicarbonate or acetate-free
solution is recommended in patients with metabolic
alkalosis.
Optimal Plan

 4.a. What drug, dosage form, dose, schedule, and duration of
therapy are best for this patient?
 IV hydration with 0.9% sodium chloride solution is the first line
therapy for this patient.
 Furosemide therapy should be discontinued until the metabolic
alkalosis has been resolved
 Potassium chloride supplementation should be initiated at a
dose of 20–40 mEq per day, patient requirements may increase
or decrease as volume depletion resolves and furosemide is
reinitiated. Potassium supplementation may be either given
orally in divided doses or added to the sodium chloride
solution (i.e., 20–40 mEq/L) and given as a constant infusion.
Further monitoring of serum potassium should continue to
ensure that overcorrection has not occurred.
Optimal Plan

 4.b. What other modifications to the patient’s current
drug regimen are warranted? Include your rationale.
 decrease the dose of the furosemide to 20 mg
daily after the metabolic alkalosis has been resolved and the
volume depletion has been corrected.
 Discontinue calcium carbonate to avoid hypercalcemia
which may affect acid/base balance toward alkaline and
as aresult there can be a loss of kedney function; (milkalkali syndrome).
Outcome Evaluation

 5.a. What clinical and laboratory parameters are necessary
to evaluate the therapy for achievement of the desired
outcome and prevention of adverse effects?
 Obtain repeat arterial blood gas in 24 hours and reassess
treatment response.
 Obtain serum electrolytes (i.e. sodium, potassium,
chloride,and bicarbonate), BUN, and serum creatinine
every12 hours for the first 24 hours and then reassess.
 Obtain vital signs every 4 hours.
Outcome Evaluation

 Obtain repeat set of urine electrolytes (i.e., sodium,
potassium,chloride) :
✓Urine sodium when a patient is euvolemic is generally
>40 mEq/L.
✓Urine potassium concentration should be between 20 and
30 mEq/L.
✓Urine chloride concentration should be between 25 and
40 mEq/L.
 Measure fluid intake and urine output every 2 hours for
24 hours, and then once every shift.