Physiology, Metabolic Alkalosis


Article Author:
Joshua Brinkman


Article Editor:
Sandeep Sharma


Editors In Chief:
Linda Lindsay


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Hajira Basit
Phillip Hynes


Updated:
3/4/2019 10:57:09 AM

Introduction

Normal human physiological pH is 7.35 to 7.45. A decrease in pH below this range is acidosis, an increase over this range is alkalosis. Metabolic alkalosis is defined as a disease state where the body’s pH is elevated to greater than 7.45 secondary to some metabolic process. Before going into details about pathology and this disease process, some background information about the physiological pH buffering process is important. The primary pH buffer system in the human body is the bicarbonate (HCO3)/carbon dioxide (CO2) chemical equilibrium system. Where:

  • H + HCO3 <--> H2CO3 <--> CO2 + H2O

HCO3 functions as an alkalotic substance. CO2 functions as an acidic substance. Therefore, increases in HCO3 or decreases in CO2 will make blood more alkalotic. The opposite is also true where decreases in HCO3 or an increase in CO2 will make blood more acidic. CO2 levels are physiologically regulated by the pulmonary system through respiration, whereas the HCO3 levels are regulated through the renal system with reabsorption rates. Therefore, metabolic alkalosis is an increase in serum HCO3.[1][2]

Related Testing

An arterial blood gas is a laboratory test used for the measurement of arterial pH, the arterial partial pressure of oxygen (PaO2), the arterial partial pressure of carbon dioxide (PaCO2), bicarbonate (HCO3), base excess, total CO2, and O2 saturation.

A venous blood gas is a laboratory test identical to an arterial blood gas measurement, except the blood is drawn from a venous site. This results in a slightly more acidic “normal” pH range.

Urine chloride is a direct measurement of chloride being excreted into urine. This test is useful to help determine the etiology of metabolic alkalosis.[3][4][5]

Pathophysiology

There is a multitude of disease states that induce metabolic alkalosis. In general, the causes can be narrowed down to an intracellular shift of hydrogen ions, gastrointestinal (GI) loss of hydrogen ions, excessive renal hydrogen ion loss, retention or addition of bicarbonate ions, or volume contraction around a constant amount of extracellular bicarbonate known as contraction alkalosis. All of which leads to the net result of increased levels of bicarbonate in the blood. As long as renal function is maintained, excess bicarbonate is excreted in the urine fairly rapidly. As a result, metabolic alkalosis will persevere if the ability to eliminate bicarbonate is impaired due to one of the following causes: hypovolemia, reduced effective arterial blood volume, chloride depletion, hypokalemia, reduced glomerular filtration rate, and/or hyperaldosteronism.

Intracellular Shift of Hydrogen

Anytime that hydrogen ions are shifted intracellularly, this imbalance in the buffer system has a relative increase in bicarbonate. Processes that drive hydrogen intracellularly include hypokalemia.

Gastrointestinal Loss of Hydrogen

Stomach fluids are highly acidic at a pH of approximately 1.5 to 3.5.  Hydrogen secretion is accomplished via parietal cells in the gastric mucosa. Therefore, the large volume loss of gastric secretions will correlate as a loss of hydrogen chloride, an acidic substance, leading to a relative increase in bicarbonate in the blood, thus driving alkalosis.  Losses can occur pathologically via vomitus or nasogastric suctioning.

Renal Loss of Hydrogen

Hydrogen is used within the kidneys are an antiporter energy gradient to retain a multitude of other elements. Of interest here, sodium is reabsorbed through an exchange for hydrogen in the renal collecting ducts under the influence of aldosterone. Therefore, pathologies that increase the levels of mineralocorticoids or increase the effect of aldosterone, such as Conn syndrome will lead to hypernatremia, hypokalemia, and hydrogen loss in the urine. In a similar vein of thought, loop and thiazide diuretics are capable of inducing secondary hyperaldosteronism by increasing sodium and fluid load to the distal nephron, which encourages the renin-angiotensin-aldosterone system.  Genetic defects that lead to decreased expression of ion transporters in the Loop of Henle are possible but less common. These syndromes are known as Bartter and Gitelman disease. The net effect of these genetic defects is akin to the action of loop diuretics.

Retention/Addition of Bicarbonate

Several etiologies lead to increases in bicarbonate within the blood. The simplest of which is an overdose of exogenous sodium bicarbonate in a medical setting. Milk-alkali syndrome is a pathology where the patient consumes excessive quantities of oral calcium antacids, which leads to hypercalcemia and varying degrees of renal failure. Additionally, since antacids are neutralizing agents, they add alkaline substances to the body while reducing acid levels thus increasing pH. A pathology that is in line with normal physiology is the body’s natural compensation mechanism for hypercarbia. When a patient hypoventilates, CO2 retention occurs in the lungs and subsequently reduces pH.  Over time, the renal system compensates by retaining bicarbonate to balance pH. This is a slower process.  Once the hypoventilation is corrected, such as with a ventilator-assisted respiratory failure patient CO2 levels will quickly decrease, but bicarbonate levels will lag in reducing. This causes post-hypercapnia metabolic alkalosis, which is self-correcting. It is possible to calculate the expected pCO2 in the setting of metabolic alkalosis to determine if it is a compensatory increase in bicarbonate, or if there is an underlying pathology driving alkalosis using the following equation:

  • Expected pCO2 = 0.7 (HCO3) + 20 mmHg +/- 5

If the expected pCO2 does not match the measured value, an underlying metabolic alkalosis is a likely present.

Contraction Alkalosis

This phenomenon occurs when a large volume of sodium-rich, bicarbonate low fluid is lost from the body. This occurs with diuretic use, cystic fibrosis, congenital chloride diarrhea, among others. The net concentration of bicarbonate increases as a result. This pathology is easily offset by the release of hydrogen from intracellular space to balance the pH in most incidences.

The exact etiology, if unknown or not obvious, can be elucidated in part by evaluation of urinary chloride. Metabolic alkalosis is split into 2 main categories: Chloride responsive with urine chloride less than 10 mEq/L and chloride resistant with urine chloride greater than 20 mEq/L.  Chloride responsive etiologies include loss of hydrogen via the gastrointestinal tract, congenital chloride diarrhea syndrome, contraction alkalosis, diuretic therapy, post-hypercapnia syndrome, cystic fibrosis, and exogenous alkalotic agent use. Chloride-resistant etiologies include retention of bicarbonate, the shift of hydrogen into intracellular spaces, hyperaldosteronism, Bartter syndrome, and Gitelman syndrome.[6][7][8][9][10][11]

Clinical Significance

Metabolic alkalosis is a relatively common diagnosis in medicine. The biological effects of metabolic alkalosis are directly resultant to associated problems such as hypovolemia and potassium and chloride depletion. These changes lead to decreased myocardial contractility, arrhythmias, decreased cerebral blood flow, confusion, increased neuromuscular excitability, and impaired peripheral oxygen unloading secondary to the shift of the oxygen dissociation curve to left.  Additionally, there is a compensatory increase in arterial pCO through hypoventilation. Overall there is a net effect on the body resulting in hypoxia.

Clinically it is important to understand the relationships between carbon dioxide and bicarbonate in the buffering system and to understand the interactions of how these components are regulated. Additionally, it is essential to understand the mechanism through which sodium, potassium, and hydrogen function to modulate pH when these ion channels are altered with medications. Therefore, the treatment of chloride resistant metabolic alkalosis is focused on treating the underlying condition that triggered the alkalotic event. Since many of these pathologies are resultant to the effect on the renin-angiotensin-aldosterone system, treatment includes inhibiting the effect of aldosterone on the nephron using potassium-sparing diuretics such as amiloride and triamterene. Additionally, an investigation for a malignant source should be considered, such as with primary hyperaldosteronism and Conn syndrome. In chloride responsive metabolic alkalosis, this includes repletion of electrolytes, specifically chloride and potassium along with the replenishment of fluid. In scenarios, such as congestive heart failure (CHF) or edematous states, diuresis is essential using potassium-sparing diuretics.[12][13]


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Physiology, Metabolic Alkalosis - Questions

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In patients with metabolic alkalosis, what laboratory parameter is usually abnormal?



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Which of the following diuretics does not cause metabolic alkalosis?



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Which is not associated with prolonged vomiting?



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A patient is found to have severe metabolic alkalosis that is resistant to all conventional medical remedies. What should be the next step in this patient's management?



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Concerning acid-base balance, which of the following statements is not true?



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Harmful effects of significant alkalosis following trauma may include which of the following?



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What is the best treatment of severe metabolic alkalosis refractory to the usual treatment?



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A 47-year-old patient is brought to the emergency department with mental status changes and hypotension. His heart rate is 110 beats/min, blood pressure 85/55 mmHg, and respirations 14. He is lethargic and confused. Electrolytes show sodium is 135 meq/L, potassium 3.5 meq/L, chloride 102 meq/L, bicarbonate 22 meq/L, BUN 45 mg/dL, and creatinine 1.8 mg/dL. PO2 is 60, PCO2 is 30, and pH is 7.46. What is the acid-base disorder?



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A patient is brought to the emergency room with mental status changes and hypotension. Heart rate is 120 bpm, blood pressure is 85/55 mmHg, and respirations are 14. He is lethargic and confused. Electrolytes show sodium is 130 meq/L, potassium 2.5 meq/L, chloride 72 meq/L, bicarbonate 79 meq/L, BUN 45 mg/dL, and creatinine 1.8 mg/dL. PO2 is 60, PCO2 is 50, and pH is 7.62. What is the most likely cause of the patient's condition?



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A patient's arterial blood gas (ABG) reveals the following: pH 7.45, PO2 85 mmHg, PCO2 45 mmHg, and bicarbonate 34 milliequivalents/L. What is the ABG interpretation?



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Which of the following is not an etiology of metabolic alkalosis?



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After colon surgery, a patient has a prolonged ileus. Physical examination reveals dry mucous membranes and decreased skin turgor. ABG shows: pH 7.54, PC02 52, P02 88. BMP shows: Na 133, K 3.0, Cl 81, HCO3 41. What is the patient's acid-base abnormality?



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A patient with intractable vomiting presents with hypochloremic, hypokalemic metabolic alkalosis. Which of the following is the most appropriate treatment?



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What is a characteristic of persistent vomiting?



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Physiology, Metabolic Alkalosis - References

References

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Metabolic alkalosis., Galla JH,, Journal of the American Society of Nephrology : JASN, 2000 Feb     [PubMed]
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Adaptations to chloride-depletion alkalosis., Galla JH,Gifford JD,Luke RG,Rome L,, The American journal of physiology, 1991 Oct     [PubMed]
Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel., Wang MX,Cuevas CA,Su XT,Wu P,Gao ZX,Lin DH,McCormick JA,Yang CL,Wang WH,Ellison DH,, Kidney international, 2018 Jan 6     [PubMed]
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Stimson L,Reynolds T, Differential diagnosis for chronic hypokalaemia. BMJ case reports. 2018 Jun 5;     [PubMed]
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