Alkalemia: (↑ arterial pH) + ↑ in plasma bicarbonate. 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.

pathophysiology

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.


↑ 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:

1.volume-mediated processes (NaCl –

responsive) 2.volume-independent processes (NaCl –

resistant) that are predominantly associated with excess mineralocorticoid activity & hypokalemia


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.


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

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.

Clinical Presentation

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.

compensation

Metabolic Alkalosis

THE CASE

Chief Complaint

“I can’t stop throwing up.”

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.

HPI

Hypertension × 20 years Hyperlipidemia Chronic kidney disease (SCr 2.2 mg/dL 1 year

ago); has never been on dialysis

PMH

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.

FH

“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.

SH

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.

ROS

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)

Meds

GenThe patient is ill-appearing and feels warm to the touch VSBP 155/89, HR 82, RR 19, T 39.8°C; Wt 80 kg, Ht 5'9''; O2 sat 97% on RA SkinSoft, intact, warm, dry HEENTEOMI; PERRLA; sclerae anicteric; funduscopic exam shows AVnicking; no sinus tenderness; dry mucous membranes; no orallesions; nasal congestion present

Physical Examination

Neck/Lymph NodesNo JVD or bruits; no lymphadenopathy or thyromegaly ChestLungs CTA bilaterally CVRRR; normal S1, S2, no S3, or S4; no murmurs, rubs, gallops AbdSoft, NTND; (+) bowel sounds GUNoncontributory


ExtDistal pulses 2+ bilaterally; femoral pulses 2+ bilaterally NeuroA & O × 3. UE strength 3/5, LE strength 3/5. CNs II–XII intact.Babinski negative bilaterally.


Labs

ABGpH 7.51, pCO2 48 mm Hg, pO2 85 mm Hg on RA UAUrine sodium 13 mEq/L; potassium 10 mEq/L; chloride 9 mEq/L Chest X-RayUnremarkable ECGNormal

Admit patient for flu-like symptoms, acute-on-

chronic kidney disease, electrolyte abnormalities, and metabolic alkalosis.

Assessment

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.


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


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


Decreased serum potassium Urine chloride <10 mEq/L Elevated urine potassium Elevated urine pH


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


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)


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

Desired Outcome

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).


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.


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.


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.


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 mgdaily 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; (milk-alkali syndrome).

Optimal Plan

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.

Outcome Evaluation

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Alkalemia: (↑ arterial pH) + ↑ in plasma bicarbonate. pathophysiology