Metabolic acidosis

Metabolic acidosis is a disorder of the acid-base balance, manifested by low blood pH values and low blood bicarbonate concentrations. In the practice of a therapist, metabolic acidosis is one of the most common disorders of the acid-base balance. Metabolic acidosis with a high and normal anion gap is distinguished depending on the presence or absence of unmeasured anions in the plasma.

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Causes metabolic acidosis

Causes include accumulation of ketones and lactic acid, kidney failure, medications or toxins (high anion gap), and gastrointestinal or renal losses of HCO3~ (normal anion gap).

The development of metabolic acidosis is based on two main mechanisms: H ⁺ load (with excess acid intake) and loss of bicarbonates or the use of HCO3 _as a buffer to neutralize non-volatile acids.

Increased H ⁺ intake into the body with insufficient compensation leads to the development of two types of metabolic acidosis: hyperchloremic and acidosis with high anion deficiency.

This acid-base imbalance develops in situations where the source of increased H ⁺ intake into the body is hydrochloric acid (HCl) - as a result, extracellular bicarbonates are replaced by chlorides. In these cases, an increase in blood chlorides above normal values causes an equivalent decrease in bicarbonate concentration. The anion gap values do not change and correspond to normal values.

High anion deficit acidosis develops when the increased intake of H ⁺ ions into the body is caused by other acids (lactic acid in lactic acidosis, ketonic acids in diabetes mellitus and starvation, etc.). These organic acids replace bicarbonate, which leads to an increase in the anion gap (AG). An increase in the anion gap by each meq/l will lead to a corresponding decrease in the concentration of bicarbonates in the blood.

It is important to note that there are close relationships between the acid-base balance and potassium homeostasis: with the development of acid-base balance disorders, there is a transition of K ⁺ from the extracellular space to the intracellular space or vice versa. With a decrease in blood pH by every 0.10 units, the concentration of K ⁺ in the blood serum increases by 0.6 mmol / l. For example, in a patient with a pH (blood) of 7.20, the concentration of K ⁺ in the blood serum increases to 5.2 mmol / l. In turn, hyperkalemia can lead to the development of acid-base balance disorders. High potassium content in the blood causes acidosis due to a decrease in the excretion of acids by the kidneys and inhibition of the formation of ammonium anion from glutamine.

Despite the close links between the acid-base balance and potassium, its metabolic disorders are not clearly manifested clinically, which is associated with the inclusion of such additional factors that affect the concentration of K ⁺ in the blood serum, such as the state of the kidneys, the activity of protein catabolism, the concentration of insulin in the blood, etc. Therefore, in a patient with severe metabolic acidosis, even in the absence of hyperkalemia, the presence of potassium homeostasis disorders should be assumed.

Main causes of metabolic acidosis

High anion gap

• Ketoacidosis (diabetes, chronic alcoholism, malnutrition, starvation).
• Lactic acidosis.
• Renal failure.
• Toxins metabolized into acids:
• Methanol (formate).
• Ethylene glycol (oxalate).
• Paraacetaldehyde (acetate, chloroacetate).
• Salicylates.
• Toxins causing lactic acidosis: CO, cyanide, iron, isoniazid.
• Toluene (initially high anion gap, subsequent excretion of metabolites normalizes the gap).
• Rhabdomyolysis (rare).

Normal anion gap

• Gastrointestinal losses of NSO - (diarrhea, ileostomy, colostomy, intestinal fistulas, use of ion exchange resins).
• Ureterosigmoidostomy, ureteroileal drainage.
• Renal losses of HCO3
• Tubulointerstitial kidney disease.
• Renal tubular acidosis, types 1,2,4.
• Hyperparathyroidism.
• Taking acetazolamide, CaCI, MgSO4.

Other

• Hypoaldosteronism.
• Hyperkalemia.
• Parenteral administration of arginine, lysine, NH CI.
• Rapid administration of NaCI.
• Toluene (late manifestations)

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Hyperchloremic metabolic acidosis

Causes of hyperchloremic metabolic acidosis

• Exogenous load of hydrochloric acid, ammonium chloride, arginine chloride. Occurs when acidic solutions (hydrochloric acid, ammonium chloride, methionine) enter the body.
• Loss of bicarbonates or dilution of blood. Most often observed in gastrointestinal diseases (severe diarrhea, pancreatic fistula, ureterosigmoidostomy), when extracellular bicarbonates are replaced by chlorides (milliequivalent per milliequivalent), since the kidneys retain sodium chloride, striving to maintain the volume of extracellular fluid. In this variant of acidosis, the anion gap (AG) always corresponds to normal values.
• Reduced acid secretion by the kidney. In this case, impaired renal bicarbonate reabsorption is also observed. The listed changes develop due to impaired H ⁺ secretion in the renal tubules or with insufficient aldosterone secretion. Depending on the level of impairment, a distinction is made between renal proximal tubular acidosis (PTA) (type 2), renal distal tubular acidosis (DTA) (type 1), and type 4 tubular acidosis with insufficient aldosterone secretion or resistance to it.

Proximal renal tubular metabolic acidosis (type 2)

The main cause of proximal tubular acidosis is considered to be a violation of the ability of the proximal tubules to maximally reabsorb bicarbonates, which leads to their increased flow into the distal part of the nephron. Normally, the proximal tubules reabsorb the entire filtered amount of bicarbonate (26 mEq/L), with proximal tubular acidosis - less, which leads to the excretion of excess bicarbonate in the urine (urine is alkaline). The inability of the kidneys to fully reabsorb it leads to the establishment of a new (lower) level of bicarbonate in the plasma, which determines the decrease in blood pH. This newly established level of bicarbonates in the blood is now completely reabsorbed by the kidney, which is manifested by a change in the urine reaction from alkaline to acidic. If, under these conditions, bicarbonate is administered to the patient so that its values in the blood correspond to normal, the urine will again become alkaline. This reaction is used to diagnose proximal tubular acidosis.

In addition to the bicarbonate reabsorption defect, patients with proximal tubular acidosis often have other changes in proximal tubule function (impaired reabsorption of phosphates, uric acid, amino acids, glucose). The concentration of K ⁺ in the blood is usually normal or slightly reduced.

The main diseases in which proximal tubular acidosis develops:

• Fanconi syndrome, primary or within the framework of genetic family diseases (cystinosis, Westphal-Wilson-Konovalov disease, tyrosinemia, etc.),
• hyperparathyroidism;
• kidney diseases (nephrotic syndrome, multiple myeloma, amyloidosis, Gougerot-Sjogren syndrome, paroxysmal nocturnal hemoglobinuria, renal vein thrombosis, medullary cystic kidney disease, after kidney transplantation);
• taking diuretics - acetazolamide, etc.

Distal renal tubular metabolic acidosis (type 1)

In distal renal tubular acidosis, in contrast to proximal tubular acidosis, the ability to reabsorb bicarbonate is not impaired, but there is a decrease in the secretion of H ⁺ in the distal tubules, as a result of which the urine pH does not decrease below 5.3, while the minimum urine pH values are normally 4.5-5.0.

Due to dysfunction of the distal tubules, patients with distal renal tubular acidosis are unable to completely excrete H ⁺, which leads to the need to neutralize the hydrogen ions formed during metabolism at the expense of plasma bicarbonate. As a result, the level of bicarbonate in the blood most often decreases slightly. Often, patients with distal renal tubular acidosis do not develop acidosis, and this condition is called incomplete distal renal tubular acidosis. In these cases, the excretion of H ⁺ occurs completely due to the compensatory reaction of the kidneys, manifested in increased formation of ammonia, which removes excess hydrogen ions.

Patients with distal renal tubular acidosis usually develop hypokalemia and associated complications (growth retardation, tendency to nephrolithiasis, nephrocalcinosis).

The main diseases in which distal renal tubular acidosis develops are:

• systemic diseases of connective tissue (chronic active hepatitis, primary liver cirrhosis, thyroiditis, fibrosing alveolitis, Gougerot-Sjogren syndrome);
• nephrocalcinosis against the background of idiopathic hypercalciuria; hyperthyroidism; vitamin D intoxication; Westphal-Wilson-Konovalov disease, Fabry disease; kidney diseases (pyelonephritis; obstructive nephropathy; transplant nephropathy); drug use (amphotericin B, analgesics; lithium preparations).

For differential diagnosis of proximal renal tubular acidosis and distal renal tubular acidosis, bicarbonate and ammonium chloride loading tests are used.

In a patient with proximal renal tubular acidosis, urine pH increases with bicarbonate administration, but this does not occur in a patient with distal renal tubular acidosis.

An ammonium chloride load test (see "Examination Methods") is performed if the acidosis is moderate. The patient is given ammonium chloride at a dose of 0.1 g/kg of body weight. Within 4-6 hours, the bicarbonate concentration in the blood decreases by 4-5 mEq/L. In patients with distal renal tubular acidosis, urine pH remains above 5.5, despite the decrease in plasma bicarbonate content; with proximal renal tubular acidosis, as in healthy individuals, urine pH decreases to less than 5.5 (usually below 5.0).

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Tubular metabolic acidosis due to insufficient aldosterone secretion (type 4)

Hypoaldosteronism, as well as impaired sensitivity to aldosterone, are considered as the cause of the development of proximal renal tubular acidosis, which always occurs with hyperkalemia. This is explained by the fact that aldosterone normally increases the secretion of both K- and H-ions. Accordingly, with insufficient production of this hormone, even under conditions of normal SCF, hyperkalemia and impaired acidification of urine are detected. When examining patients, hyperkalemia is detected that does not correspond to the degree of renal failure, and an increase in urine pH with an impaired response to ammonium chloride load (as in distal renal tubular acidosis).

The diagnosis is confirmed by finding low serum aldosterone and renin levels. In addition, serum aldosterone levels do not increase in response to sodium restriction or volume depletion.

The presented symptom complex is known as the syndrome of selective hypoaldosteronism or, when reduced renin production by the kidneys is simultaneously detected, as hyporeninemic hypoaldosteronism with hyperkalemia.

Causes of the syndrome development:

• kidney damage, especially in the stage of chronic renal failure,
• diabetes mellitus,
• medications - NSAIDs (indomethacin, ibuprofen, acetylsalicylic acid), sodium heparin;
• involutional changes in the kidneys and adrenal glands in old age.

High anion gap metabolic acidosis

AP (anion gap) is the difference between the concentrations of sodium and the sum of the concentrations of chlorides and bicarbonate:

AP = [Na ⁺ ] - ([Cl~] + [HCO3]).

Na ⁺, Cl~, HCO ₃ ~ are found in the extracellular fluid in the highest concentrations. Normally, the concentration of sodium cation exceeds the sum of chloride and bicarbonate concentrations by approximately 9-13 meq/l. The lack of negative charges is usually covered by negatively charged blood proteins and other unmeasured anions. This gap is defined as the anion gap. Normally, the anion gap is 12±4 mmol/l.

When undetectable anions (lactate, keto acids, sulfates) increase in the blood, bicarbonate is replaced by them; accordingly, the sum of anions ([Cl~] + [НСO3 _~ ]) decreases and the value of the anion gap increases. Thus, the anion gap is considered an important diagnostic indicator, and its determination helps to establish the causes of the development of metabolic acidosis.

Metabolic acidosis, which is caused by the accumulation of organic acids in the blood, is characterized as high-AP metabolic acidosis.

Causes of development of high anion gap metabolic acidosis:

• ketoacidosis (diabetes mellitus, starvation, alcohol intoxication);
• uremia;
• intoxication with salicylates, methanol, toluene and ethylene glycol;
• lactic acidosis (hypoxia, shock, carbon monoxide poisoning, etc.);
• paraldehyde poisoning.

Ketoacidosis

It usually develops with incomplete oxidation of free fatty acids to CO2 _and water, which leads to increased formation of beta-hydroxybutyric and acetoacetic acid. Most often, ketoacidosis develops against the background of diabetes mellitus. With a lack of insulin and increased formation of glucagon, lipolysis increases, which leads to the entry of free fatty acids into the blood. At the same time, the formation of ketone bodies in the liver increases (the concentration of plasma ketones exceeds 2 mmol / l). The accumulation of keto acids in the blood leads to their replacement of bicarbonate and the development of metabolic acidosis with an increased anion gap. A similar mechanism is also revealed during prolonged starvation. In this situation, ketones replace glucose as the main source of energy in the body.

Lactic acidosis

It develops with increased concentrations of lactic acid (lactate) and pyruvic acid (pyruvate) in the blood. Both acids are normally formed during glucose metabolism (Krebs cycle) and are utilized by the liver. In conditions that increase glycolysis, the formation of lactate and pyruvate increases sharply. Lactic acidosis most often develops in shock, when, due to decreased oxygen supply to tissues under anaerobic conditions, lactate is formed from pyruvate. Lactic acidosis is diagnosed when increased lactate levels are detected in the blood plasma and metabolic acidosis with a large anion gap is identified.

Acidosis in poisoning and intoxication

Intoxication with drugs (acetylsalicylic acid, analgesics) and substances such as ethylene glycol (antifreeze component), methanol, toluene, can also lead to the development of metabolic acidosis. The source of H ⁺ in these situations is salicylic and oxalic acid (in case of ethylene glycol poisoning), formaldehyde and formic acid (in case of methanol intoxication). The accumulation of these acids in the body leads to the development of acidosis and an increase in the anion gap.

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Uremia

Severe renal failure and especially its terminal stage are often accompanied by the development of metabolic acidosis. The mechanism of development of acid-base balance disorders in renal failure is complex and varied. As the severity of renal failure increases,

The initial factors that caused metabolic acidosis may gradually lose their dominant role, and new factors are included in the process, which become leading ones.

Thus, in moderate chronic renal failure, the main role in the development of acid-base balance disorders is played by a decrease in the total excretion of acids due to a decrease in the number of functioning nephrons. There is not enough ammonia to remove the daily endogenous production of H ⁺ formed in the renal parenchyma, as a result of which some of the acids are neutralized by bicarbonate (changes characteristic of renal distal tubular acidosis).

On the other hand, at this stage of chronic renal failure, there may be a disruption in the ability of the kidneys to reabsorb bicarbonate, which leads to the development of acid-base balance disorders such as renal distal tubular acidosis.

With the development of severe renal failure (SCF about 25 ml/min), the main factor in the development of acidosis becomes the retention of organic acid anions (sulfates, phosphates), which determines the development of acidosis in patients with high AP.

A certain contribution to the development of acidosis is also made by hyperkalemia developing in ESRD, which aggravates the disturbance of acid excretion due to the inhibition of the formation of ammonium from glutamine.

If hypoaldosteronism develops in patients with chronic renal failure, the latter intensifies all manifestations of acidosis due to both an even greater decrease in H ⁺ secretion and hyperkalemia.

Thus, in chronic renal failure, all variants of metabolic acidosis development can be observed: hyperchloremic acidosis with normokalemia, hyperchloremic acidosis with hyperkalemia, acidosis with an increased anion gap.

Symptoms metabolic acidosis

Symptoms and signs in severe cases include nausea, vomiting, drowsiness, hyperpnea. Diagnosis is based on clinical findings and arterial blood gas measurements and plasma electrolyte levels. The underlying cause should be treated; if the pH is very low, intravenous NaHCO3 may be indicated.

Symptoms of metabolic acidosis depend largely on the underlying cause. Mild acidemia is usually asymptomatic. More severe acidemia (pH < 7.10) may cause nausea, vomiting, and fatigue. Symptoms may also occur at higher pH levels if acidosis develops rapidly. The most characteristic sign is hyperpnea (deep breaths at a normal rate), reflecting a compensatory increase in alveolar ventilation.

Severe acute acidemia predisposes to the development of cardiac dysfunction with hypotension and shock, ventricular arrhythmias, coma. Chronic acidemia causes bone demineralization (rickets, osteomalacia, osteopenia).

Diagnostics metabolic acidosis

Identifying the cause of metabolic acidosis begins with determining the anion gap.

The cause of a high anion gap may be clinically obvious (eg, hypovolemic shock, missed hemodialysis session), but if the cause is unknown, blood tests should be performed to determine glucose, blood urea nitrogen, creatinine, lactate for toxins. Most labs measure salicylates, methanol and ethylene glycol levels are not always determined, their presence can be assumed by the presence of an osmolar gap.

The calculated serum osmolarity (2[Na] + [glucose]/18 + blood urea nitrogen/2.8 + blood alcohol/5) is subtracted from the measured osmolarity. A difference of more than 10 indicates the presence of osmotically active substances, which in the case of high anion gap acidosis are methanol or ethylene glycol. Although ethanol ingestion can cause an osmolar gap and mild acidosis, it should not be considered a cause of significant metabolic acidosis.

If the anion gap is within normal limits and there is no obvious cause (eg, diarrhea), electrolyte levels should be determined and the urinary anion gap calculated ([Na] + [K] - [CI] is normally 30-50 mEq/L, including in patients with gastrointestinal losses). An increase suggests renal losses of HCO3.

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Treatment metabolic acidosis

Treatment is aimed at correcting the underlying cause. Hemodialysis is necessary in cases of renal failure, and sometimes in cases of poisoning with ethylene glycol, methanol, and salicylates.

Correction of acidemia with NaHCO3 is indicated only in certain circumstances and is unsafe in others. When metabolic acidosis is due to loss of HCO3 or accumulation of inorganic acids (i.e., normal anion gap acidosis), HCO3 therapy is reasonably safe and adequate. However, when acidosis is due to accumulation of organic acids (i.e., high anion gap acidosis), the data on the use of HCO3 are conflicting; in such cases, there is no proven improvement in mortality and certain risks are involved.

In the treatment of the initial state, lactates and keto acids are metabolized to HCO3, so the introduction of exogenous HCO3 can lead to excess and metabolic alkalosis. In any state, HCO3 can also lead to excess Nan, hypervolemia, hypokalemia, and hypercapnia, by suppressing the respiratory center. Moreover, since HCO3 does not penetrate cell membranes, there is no correction of intracellular acidosis, on the contrary, a paradoxical deterioration can be observed, since part of the introduced HCO3 is converted to CO2, which penetrates into the cell and is hydrolyzed to H and HCO3.

An alternative to NaHCO3 is tromethamine, an amino alcohol that binds both metabolic (H) and respiratory (HCO3) acids; carbicarb, an equimolar mixture of NaHCO3 and carbonate (the latter reacts with CO2 to form O2); dichloroacetate, which stimulates lactate oxidation. However, the effectiveness of these substances is unproven and they can also lead to various complications.

Potassium deficiency, which is often observed in metabolic acidosis, should also be corrected by oral or parenteral administration of KCI.

Thus, treatment of metabolic acidosis consists of eliminating the disorders caused by this pathological process, mainly by administering an adequate amount of bicarbonates. If the cause of metabolic acidosis is eliminated on its own, treatment with bicarbonate is not considered necessary, since normally functioning kidneys are able to restore bicarbonate reserves in the body on their own within a few days. If metabolic acidosis cannot be eliminated (for example, chronic renal failure), long-term treatment of metabolic acidosis is necessary.