Metabolic alkalosis

What is metabolic alkalosis?

Metabolic alkalosis is an abnormal increase in the pH of tissues in the body. Among these, the blood and - consequently - the urine are particularly involved.

Metabolic alkalosis is an acid-base disorder frequently encountered in hospitalized patients, especially those in critical conditions, and is often complicated by mixed acid-base disorders (later on we will better understand what it is).

This disorder can have serious clinical consequences, particularly on the cardiovascular and central nervous system. The severity level is partly determined by the effectiveness / efficiency of the organism's compensation system.

At the base of metabolic alkalosis there is a complex hydro-saline disorder, on which the onset of acid-base disorder depends.

The metabolic alkalosis can have different etiological causes, which feed on each other aggravating the condition. Since the resolution of the acid-base disorder depends on the correction of these factors, it is essential to know the specific mechanisms to undertake the most appropriate therapeutic action.

Symptoms

Symptoms of metabolic alkalosis

The main symptoms of metabolic alkalosis, mainly related to the alcalaemia, are:

• Unstoppable vomit
• Dehydration
• Confusion
• Asthenia.

Causes

Primary causes

The direct mechanism of metabolic alkalosis consists in the alteration of the blood pH; this is especially true for:

• Loss of hydrogen ions (H +), which exert an acid function, and consequent increase in bicarbonate [hydrogen-bicarbonate ions (HCO ₃ -)], which have a basic function
• Independent increase of bicarbonate.

The causes of these imbalances can be divided into two categories, depending on the level of chloride measurable in the urine.

Chlorine-responsive (urine chloride <10 mEq / L)

• Hydrogen ion loss: occurs mainly through two mechanisms, vomiting and renal filtration.
• Vomiting causes the loss of hydrochloric acid (hydrogen and chloride ions) contained in the stomach.
• Severe vomiting also causes the loss of potassium (hypokalaemia) and sodium (hyponatremia). The kidneys compensate for these losses by maintaining the sodium in the collection ducts at the expense of the hydrogen ions (saving the sodium / potassium pumps to prevent further loss of potassium), leading however to metabolic alkalosis.
• Chloride congenital diarrhea: very rare cause, because diarrhea more easily causes acidosis instead of alkalosis.
• Contraction alkalosis: caused by the loss of water in the extracellular spaces, for example due to systemic dehydration. The reduction of extracellular volumes triggers the renin-angiotensin-aldosterone system and the aldosterone subsequently stimulates the reabsorption of sodium (and therefore water) within the nephron of the kidney. However, aldosterone is also responsible for stimulating the renal excretion of hydrogen ions (considering bicarbonate), and it is this loss that increases the pH of the blood.
• Diuretic therapy: loop diuretics and thiazides may initially cause chloride increase but, once depleted, urine excretion will be less than <25 mEq / L. Fluid loss due to sodium excretion causes contraction alkalosis.
• Post-hypercapnia: hypoventilation (decrease in respiratory rate) causes hypercapnia (increase in CO2), which consequently causes respiratory acidosis. Renal compensation, which involves the release of large quantities of bicarbonate, is necessary to reduce the effect of acidosis. Once the levels of carbon dioxide return to normal, the excess of bicarbonate persists inducing the so-called metabolic alkalosis.
• Cystic fibrosis: excessive loss of sodium chloride with sweat leads to the contraction of extracellular volumes (similarly to what happens in the alkalosis by contraction) and to the exhaustion of chloride.

Chloride-resistant (urine chloride> 20 mEq / L)

• Bicarbonate retention: bicarbonate retention can lead to alkalosis.
• Hydrogen ion displacement in the intracellular space: it is the same process described in hypokalemia. Due to the low concentration in the extracellular space, potassium moves into the cells. To maintain electrical neutrality, hydrogen also follows the same path, consequently increasing the blood pH.
• Alkalizing agents: alkalizing agents, such as bicarbonate (given in cases of peptic ulcer or hyperacidity) and antacids, in excessive doses can lead to alkalosis.
• Hyperaldosteronism: an excess of aldosterone (typical of the Conn syndrome - adrenal adenoma) causes the loss of hydrogen ions in the urine by increasing the activity of the sodium-hydrogen exchange protein in the kidney. This increases the retention of sodium ions, while hydrogen ions are pumped into the renal tubule. Excess sodium increases the extracellular volume and the loss of hydrogen ions creates metabolic alkalosis. Later, the kidney reacts through the excretion of aldosterone in order to expel sodium and chloride in the urine.
• Excessive consumption of Glycyrrhizin (active ingredient of licorice extract)
• Bartter syndrome and Gitelman syndrome, two diseases with similar treatments consisting of the coupling of diuretics even in normotensive patients.
• Liddle syndrome: a mutation of the functions in the genes that code for the epithelial sodium channel (ENaC) characterized by hypertension and hypoaldosteronism.
• Deficiency of 11β-hydroxylase and 17α-hydroxylase: both characterized by hypertension.
• The toxicity of the aminoglycoside can induce hypokalemic metabolic alkalosis by activating the calcium receptor in the ascending nephron tract, inactivating the NKCC2 transporter, in a manner similar to that of Bartter.

Clinical causes

NaCl-sensitive (with volume contraction)

• He retched
• Nose-gastric tube
• Diuretic therapy
• Post-hypercapnia
• Chlorine-dispersing enteropathies

NaCl-resistant (with volume expansion)

• Primary hyperaldosteronism
• Cushing syndrome
• Exogenous steroids or drugs with mineralocorticoid activity
• Secondary hyperaldosteronism (renal artery stenosis, accelerated hypertension, renin-secreting tumors)
• Deficiency 11- or 12-adrenal hydroxylase
• Liddle syndrome

Administration or ingestion of alkalis

• Milk-alkaline syndrome
• HCO ₃ - oral or parenteral in renal failure
• Conversion of HCO ₃ precursors - after organic acidosis

Different

• Feeding after fasting
• Hypercalcemia with secondary hyperparathyroidism
• High-dose penicillins
• Serious deficiency of K + or Mg ++
• S. of Bartter

Compensation

Physiological compensation of metabolic alkalosis

In its pure form, metabolic alkalosis manifests itself as alcalemia and consequent alveolar hypoventilation (reduction of respiratory rate). This is aimed at increasing the pressure of carbon dioxide (PaCO2) in the arteries, which is in turn necessary for the formation of carbonic acid, which is essential for controlling the change in pH. Normally, arterial PaCO2 increases by 0.5-0.7 mmHg for every 1 mEq / L of plasma bicarbonate and is very fast.

Respiratory compensation, however, is an incomplete reaction. Hydrogen reduction suppresses peripheral chemoreceptors sensitive to pH change. The increase in pCO2 (caused by hypoventilation) can stimulate the compensation intervention by central chemoreceptors, which are very sensitive to the variation of the partial pressure of carbon dioxide in the cerebrospinal fluid. Precisely because of this reaction, the respiratory rate may increase again.

The renal compensation of the metabolic alkalosis is less effective than the respiratory compensation and consists in a greater excretion of bicarbonate, overcoming the ability of the renal tubule to reabsorb it.

Diagnosis

Diagnosis of metabolic alkalosis

Blood test: electrolyte and gas dosage

Recognized the typical symptoms of metabolic alkalosis, the actual diagnosis is made by measuring the concentration of electrolytes and gases dissolved in arterial blood. Among these, the level of HCO ₃ - which generally tends to increase significantly - is particularly important. It is however necessary to remember that the increase in blood bicarbonate is not a prerogative of metabolic alkalosis; on the contrary, it also manifests itself in the compensatory response to primary type respiratory acidosis.

We could define that, if the concentration of HCO ₃ - reaches or exceeds 35 mEq / L, there is a very high probability that it is metabolic alkalosis.

Differential diagnosis: urinalysis

When the etiology of metabolic alkalosis is uncertain and the use of drugs or arterial hypertension is suspected, it may be necessary to perform other analyzes. First of all, the dosage of chloride ions (Cl-) in urine and the calculation of the gap related to the concentration of serum anions. This last parameter is fundamental to differentiate the primary metabolic alkalosis from the compensation of the respiratory acidosis.

Consequences

Clinical consequences

The clinical consequences of metabolic alkalosis are:

• Cardiovascular
• Aronal constriction
• Decreased coronary flow
• Lowering of the anginal threshold
• Supraventricular and ventricular arrhythmias
• respiratory
• Hypoventilation, hypercapnia, hypoxemia
• metabolic
• Stimulation of anaerobic glycolysis
• Hypokalemia
• Decrease in ionized fraction of serum calcium
• Hypomagnesemia and hypophosphatemia
• Central nervous system
• Decreased brain flow
• Tetany, convulsions, lethargy, delirium, stupor.

Complications

In the event that, for the reasons that we will see later, physiologic reactions should not prove to be quite effective or efficient, the risk of the so-called mixed acid-base disorders increases. For example, if the increase in arterial PaCO2 is greater than 0.7 per 1 mEq / L of plasma bicarbonate, the condition of metabolic alkalosis may arise in association with primary respiratory acidosis. Similarly, if the increase in PaCO2 is lower, primary respiratory alkalosis occurs in addition to the metabolic alkalosis.

Therapy

The management of metabolic alkalosis depends above all on the etiology and conditions of the subject. In some cases it is necessary to intervene directly on the alkalosis, injecting an intravenous solution with an acid pH into the blood.