Metabolic acidosis

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

[1], [2], [3], [4]

Causes of the metabolic acidosis

The reasons include the accumulation of ketones and lactic acid, renal failure, the intake of drugs or toxins (high anion gap) and gastrointestinal or renal losses HCO3 ~ (normal anion gap).  

At the heart of the development of metabolic acidosis are two main mechanisms - the load of H ⁺  (with excess acid intake) and the loss of bicarbonates or the use of HCO ₃  as a buffer to neutralize non-volatile acids.

Increased intake of H ⁺  in the body with insufficient compensation leads to the development of two variants of metabolic acidosis - hyperchloremic and acidosis with a high anionic deficiency.

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

Acidosis with a high anionic deficiency develops when the cause of increased intake of H ⁺ ions  in the body are other acids (lactate with lactic acidosis, ketonic acids in diabetes and fasting, etc.) These organic acids replace bicarbonate, which leads to an increase in the anion gap AP). The growth of the anion gap for 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 state of acid-base equilibrium and the homeostasis of potassium: with the development of violations of the acid-base state, there is a transition of K ⁺  from the extracellular space to the intracellular or backward direction. With a decrease in the pH of the blood for every 0.10 units, the concentration of K ⁺  in the serum increases by 0.6 mmol / l. For example, in a patient with a pH (blood) value of 7.20  , the serum K ⁺ concentration increases to 5.2 mmol / l. In turn, hyperkalemia can lead to the development of violations of CBS. The high content of potassium in the blood causes acidosis due to a decrease in the excretion of acid by the kidneys and inhibition of the formation of the ammonium anion from glutamine.

Despite the close links between the state of the acid-base state and potassium, the disturbances in its metabolism are not clinically manifested, which is due to the inclusion of such additional factors affecting the  serum K ⁺ concentration, such as kidneys, catabolism of proteins, the concentration of insulin in the blood , etc. Therefore, in a patient with severe metabolic acidosis, even in the absence of hyperkalemia, it is necessary to assume the presence of disturbances in potassium homeostasis.

The main causes of metabolic acidosis

High anion gap

• Ketoacidosis (diabetes, chronic alcoholism, eating disorders, starvation).
• Lactic acidosis.
• Renal failure.
• Toxins metabolized to acids:
• Methanol (formate).
• Ethylene glycol (oxalate).
• Paracetaldehyde (acetate, chloroacetate).
• Salicylates.
• Toxins that cause lactic acidosis: CO, cyanides, iron, isoniazid.
• Toluene (initially high anionic gap, subsequent excretion of metabolites normalizes the gap).
• Rhabdomyolysis (rarely).

Normal anion gap

• Gastrointestinal loss of NSO - (diarrhea, ileostoma, colonostomy, intestinal fistula, use of ion exchange resins).
• Ureterosigmoidostomy, uretheroileal drainage.
• Renal loss of HCO3
• Tubulo-interstitial kidney disease.
• Renal tubular acidosis, types 1,2,4.
• Hyperparathyroidism.
• Acetazolamide, CaCI, MgSO4.

Other

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

[5], [6], [7], [8]

Hyperchloremic metabolic acidosis

Causes of hyperchloroemic metabolic acidosis

• Exogenous loading with hydrochloric acid, ammonium chloride, arginine chloride. Occurs when acid solutions (hydrochloric acid, ammonium chloride, methionine) enter the body.
• Loss of bicarbonate or blood dilution. Most often observed in diseases of the gastrointestinal tract (severe diarrhea, pancreatic fistula, ureterosigmoidostomy), when the replacement of extracellular bicarbonates with chlorides (milliequivalent per milliequivalent), as the kidneys retain sodium chloride, aiming to maintain the volume of extracellular fluid. In this variant of acidosis, the anion gap (AP) always corresponds to normal values.
• Reducing the secretion of acid by the kidney. At the same time, a violation of the reabsorption of bicarbonate by the kidneys is also observed. The listed changes develop due to a violation of the secretion of H ⁺  in the renal tubules or with insufficient secretion of aldosterone. Depending on the level of the disorder, renal proximal tubular acidosis (PKA) (type 2), renal distal tubular acidosis (DKA) (type 1), tubular acidosis of type 4 with insufficient aldosterone secretion or resistance to it are distinguished.

Proximal renal tubular metabolic acidosis (type 2)

As a primary cause of proximal tubular acidosis, a disruption of the ability of the proximal tubules to maximize the reabsorption of bicarbonates is considered, which leads to an increased intake of them into the distal nephron section. Normally, in the proximal tubules, the entire filtered amount of bicarbonate (26 meq / L) is reabsorbed, with less proximal tubular acidosis, which results in urinary excretion of the excess bicarbonate (urine alkaline). The inability of the kidneys to completely reabsorbate leads to the establishment of a new (lower) level of bicarbonate in the plasma, which determines the decrease in the pH of the blood. This newly established level of bicarbonate in the blood is now completely reabsorbed by the kidney, which is manifested by a change in the reaction of urine from alkaline to acid. If, under these conditions, the patient is administered bicarbonate so that his blood values correspond to normal, the urine will again become alkaline. This reaction is used for the diagnosis of proximal tubular acidosis.

In addition to the defect of bicarbonate reabsorption, in patients with proximal tubular acidosis, other changes in proximal tubule function are often detected (disruption of reabsorption of phosphates, uric acid, amino acids, glucose). Concentration of K ⁺  in the blood, as a rule, normal or slightly reduced.

The main diseases in which proximal tubular acidosis develops are:

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

Distal renal tubular metabolic acidosis (type 1)

In the case of distal renal tubular acidosis, unlike proximal tubular acidosis, the ability to reabsorb bicarbonate is not impaired, but there is a decrease in H ⁺ secretion  in the distal tubules, resulting in a urinary pH of less than 5.3, while the minimum urinary pH values are normally 4.5-5.0.

Because of violations of the function of the distal tubules, patients with distal renal tubular acidosis are unable to completely isolate H ⁺, which leads to the need to neutralize the hydrogen ions formed in the process of metabolism due to plasma bicarbonate. As a result, the level of bicarbonate in the blood often decreases slightly. Often, in patients with distal renal tubular acidosis, acidosis does not develop, and this condition is called incomplete distal renal tubular acidosis. In these cases, the release of H ^{+ is}  completely due to the compensatory reaction of the kidneys, which manifests itself in the increased formation of ammonia, which removes excess hydrogen ions.

In patients with distal renal tubular acidosis, as a rule, hypokalemia occurs, concomitant complications develop (growth retardation, propensity to nephrolithiasis, nephrocalcinosis).

The main diseases in which distal tubular acidosis develops are:

• systemic connective tissue diseases (chronic active hepatitis, primary cirrhosis, thyroiditis, fibrosing alveolitis, Guzero-Sjogren's syndrome);
• nephrocalcinosis in the background of idiopathic hypercalciuria; hyperthyroidism; intoxication with vitamin D; disease of Westphalia-Wilson-Konovalov, Fabry's disease; kidney disease (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, samples with loading of bicarbonate and ammonium chloride are used.

In a patient with proximal renal tubular acidosis, with the introduction of bicarbonate, the urine pH increases, and in a patient with distal renal tubular acidosis this does not occur.

A sample with a load of ammonium chloride (see "Methods of Examination") is performed if acidosis is moderately expressed. The patient is treated with ammonium chloride at a dose of 0.1 g / kg body weight. Within 4-6 hours the concentration of bicarbonate in the blood decreases by 4-5 meq / l. In patients with distal renal tubular acidosis, the pH of urine remains above 5.5 despite a decrease in plasma bicarbonate; with proximal renal tubular acidosis in the same way as in healthy individuals, the urine pH drops below 5.5 (often below 5.0).

[9], [10], [11], [12], [13], [14], [15], [16],

Tubular metabolic acidosis with insufficient aldosterone secretion (type 4)

Hypoaldosteronism, like a violation of sensitivity to aldosterone, is considered as the cause of the development of proximal renal tubular acidosis, which always occurs with hyperkalemia. This is due to the fact that aldosterone normally increases the secretion of both K- and H-ions. Accordingly, with insufficient production of this hormone, even under normal GFR, hyperkalaemia and urinary acidification are detected. When examining patients, hyperkalemia, not corresponding to the degree of renal insufficiency, and an increase in the pH of urine with a disturbed reaction to the ammonium chloride load (as in the case of distal renal tubular acidosis) are revealed.

The diagnosis is confirmed by the detection of low values of aldosterone and renin in the blood serum. In addition, the level of aldosterone in the blood does not increase in response to sodium restriction or a decrease in the volume of circulating blood.

The presented symptom complex is known as a syndrome of selective hypoaldosteronism or, with simultaneous detection of reduced renin production by the kidneys, as giporeninemic hypoaldosteronism with hyperkalemia.

Causes of the syndrome:

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

Metabolic acidosis with high anion deficiency

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

AP = [Na ⁺ ] - ([Cl ~] + [HCO 3 ]).

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

With the increase in the blood of undetectable anions (lactate, ketoacids, sulfates), they are replaced by bicarbonate; accordingly, the sum of the anions ([Cl ~] + [HCO ₃ ~]) decreases and the value of the anion gap increases. Thus, the anion gap is considered an important diagnostic index, and its definition 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 metabolic acidosis with a high AP.

The causes of the development of metabolic acidosis with a high anion gap:

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

Ketoacidosis

It usually develops when the free fatty acids are not completely oxidized to CO ₂  and water, which leads to an increased formation of beta-hydroxybutyric acid and acetoacetic acid. Most often, ketoacidosis develops against the background of diabetes mellitus. With insulin deficiency and increased glucagon formation, lipolysis increases, which leads to free fatty acids entering the blood. Simultaneously, the formation of ketone bodies increases in the liver (the concentration of plasma ketones exceeds 2 mmol / l). The accumulation of keto acids in the blood leads to the replacement of bicarbonate and the development of metabolic acidosis with an increased anion gap. A similar mechanism is revealed even with prolonged starvation. In this situation, ketones replace glucose as the main source of energy in the body.

Lactate acidosis

It develops with a high concentration of lactic acid (lactate) and pyruvic acid (pyruvate) in the blood. Both acids are formed normally in the process of glucose metabolism (Krebs cycle) and are utilized by the liver. Under conditions that increase glycolysis, the formation of lactate and pyruvate increases sharply. Most often, lactic acidosis develops in shock, when, due to a decrease in oxygen supply to tissues under anaerobic conditions, lactate is formed from pyruvate. The diagnosis of lactate acidosis is raised when a high lactate concentration in the blood plasma is detected and metabolic acidosis with a large anion gap is detected.

Acidosis with poisoning and intoxication

Intoxications 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 (with ethylene glycol poisoning), formaldehyde and formic acid (with methanol intoxication). Accumulation of these acids in the body leads to the development of acidosis and an increase in the anion gap.

[17], [18], [19], [20], [21], [22]

Uremia

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

The initial factors that caused metabolic acidosis can gradually lose their dominant importance, and new factors become involved in the process, which become leading.

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

On the other hand, in this stage of chronic renal insufficiency, there may be a disruption of the ability of the kidneys to reabsorbate bicarbonate, which leads to the development of violations of the acid-base state by the type of renal distal tubular acidosis.

With the development of severe kidney failure (GFR about 25 ml / min), the main factor in the development of acidosis is the delay of anions of organic acids (sulfates, phosphates), which determines the development in patients with acidosis with large AP.

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

If hypoaldosteronism develops in patients with chronic renal insufficiency, the latter strengthens all manifestations of acidosis due to both a further decrease in H ⁺ secretion and hyperkalemia.

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

Symptoms of the metabolic acidosis

Symptoms and signs in severe cases include nausea, vomiting, drowsiness, hyperpnoea. Diagnosis is based on clinical data and the determination of the gas composition of arterial blood, as well as the level of plasma electrolytes. Treatment of the original cause is necessary; At a very low pH, intravenous administration of NaHCO3 can be indicated.

Symptoms of metabolic acidosis mainly depend on the underlying cause. Light acidemia usually occurs asymptomatically. With more severe acidemia (pH <7,10), nausea, vomiting, fatigue can occur. Symptoms can also occur at higher pH levels if the development of acidosis occurs quickly. The most characteristic feature is hyperpnoea (deep breaths with normal frequency), reflecting the 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 demineralization of bones (rickets, osteomalacia, osteopenia).

Diagnostics of the metabolic acidosis

The identification of the cause of metabolic acidosis begins with the definition of the anion gap.

The reason for the high anion gap may be clinically obvious (for example, hypovolemic shock, missed hemodialysis session), but for unknown reasons, blood tests should be performed   to determine the level of glucose, blood urea nitrogen, creatinine, lactate for toxins. In most laboratories, the level of salicylates is determined, methanol and ethylene glycol levels are not always determined, their presence can be assumed by the presence of an osmolar gap.

The calculated osmolality of the serum (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 acidosis with a high anionic gap, are methanol or ethylene glycol. Although ethanol intake may cause the osmolar gap and the development of mild acidosis, it should not be considered as the cause of significant metabolic acidosis.

If the anion gap is within normal limits and there is no obvious cause (for example, diarrhea), it is necessary to determine the level of electrolytes and calculate the urinary anion gap ([Na] + [K] - [CI], normal, including patients with gastrointestinal loss, 30 -50 meq / L). The increase assumes the presence of renal losses of HCO3.

[23], [24], [25], [26], [27],

Treatment of the metabolic acidosis

Treatment is aimed at correcting the original cause. Hemodialysis is necessary in case of renal failure, and also sometimes when poisoning with ethylene glycol, methanol, salicylates.

Correction of the acidemia of NaHCO3 is indicated only under certain circumstances, while in others it is unsafe. In the event that metabolic acidosis develops due to the loss of HCO3 or the accumulation of inorganic acids (i.e., acidosis with a normal anionic gap), HCO3 therapy is sufficiently safe and adequate. But if acidosis has developed due to the accumulation of organic acids (i.e., acidosis with a high anion gap), data on the use of HCO3 are inconsistent; In such cases, the improvement in the mortality rate has not been proven, and there are certain risks.

In the treatment of the initial condition, lactates and keto acids are metabolized in HCO3, so the administration of exogenous HCO3 can lead to excess and metabolic alkalosis. In any condition, HCO3 can also lead to an excess of 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, paradoxical deterioration may occur, since part of the HCO3 introduced 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, equimolar mixture of NaHCO3 and carbonate (the latter reacts with CO2 to form O2); dichloroacetate, which stimulates the oxidation of lactate. However, the effectiveness of these substances is not proven, 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, the treatment of metabolic acidosis consists in the elimination of disturbances caused by this pathological process, mainly by the introduction of an adequate amount of bicarbonates. If the cause of metabolic acidosis is eliminated on its own, bicarbonate treatment is not considered mandatory, since normally functioning kidneys are able to restore bicarbonate reserves in the body on their own for several days. If metabolic acidosis can not be eliminated (eg, chronic renal failure), long-term treatment of metabolic acidosis is necessary.