Definition and diagnosis:
Metabolic acidosis is defined by the association of an acidic blood pH (less than or equal to 7.37) with a decrease in the alkaline reserve (less than or equal to 24 mmol / L).
Clinical signs are non-specific and inconstant.
– Polypnea shows alveolar hyperventilation. This is the physiological respiratory compensation that is insufficient to correct blood pH. On gasometry, PaCO 2 decreases, while PaO 2 is normal, as is arterial saturation in oxygen. The gasometry of a metabolic acidosis is thus:
– pH < 7.37, HCO 3- < 24 mmol / L, PaCO 2 < 40 mmHg, PaO 2 > 90 mmHg, SaO 2 > 95%.
– Hypertension is related to the secretion of catecholamines. In cases of severe acidosis, myocardial depression or shock may occur.
– Neuropsychic disorders are possible: mental confusion, even coma in severe forms.
In the presence of metabolic acidosis, diagnostic behavior must be stereotyped. It is necessary to calculate the anionic (TrA) blood hole, to check the pure metabolic character of the acidosis and to calculate the urinary TRA to know the renal response to acidosis.
BLOOD ANIONIC HOLE:
Initially, blood TrA should always be determined from the ionogram.
TrA = (Na + + K + ) – (Cl – + HCO 3- )
The normal value is 12 ± 2 mmol / L (8 to 16 mmol / L). TrA consists essentially of proteinate anions (especially albumin), and somewhat by sulfates, phosphates and organic anions.
This simple calculation makes it possible to distinguish between the two major types of metabolic acidosis, acidosis with indoated anions, and hyperchloremic acidosis.
In acidosis with indoated anions, the cholera level remains normal.
This means that there is an overload, or defect in catabolism or excretion of anions that replaces Cl – .
In hyperchloremic acidosis, chloroemia rises because HCO 3
– consumed are replaced by Cl – . This means that the acid overload includes the anion Cl – or an anion removed in the urine with Na + , which leads to stimulation of the reabsorption of Cl – .
Sometimes both types of acidosis may associate: there is then an increase in TrA, while chloroemia is lower than in acidosis with indoated anions. A frequent situation is that of the patient with an acidosis with indoated anions seen while the acidosis has already benefited from a symptomatic treatment (for example perfusion of HCO 3- ). In this case, the TrA persists, while the HCO 3- has normalized.
There is no particular “trap” in the calculation of the TrA. However, some clinical situations are associated with variations, generally not significant of the TrA.
EXPECTED VALUE OF PACO 2:
The pure metabolic character of acidosis should be ascertained by calculating the expected value of PaCO 2 for the degree of acidosis observed:
¢ PaCO 2 = ¢ HCO 3- ‘ 1.25
For example: if the reserve is 16 mmol / L, the expected PaCO 2 must be 28 mmHg. The calculation is as follows:
delta HCO 3- = 26 – 16 = 10 x 1.25 = 12.5
delta PaCO 2 = 40 – 12.5 = 27.5 mmHg
If PaCO 2 is greater than 28 mmHg, there is a respiratory component to acidosis.
URINEAR URIONAL HOLE:
Urinary TrA should be determined to determine if the renal response is appropriate or not. The excretion of the acidic charge is essentially effected by NH 4 + ; its value is about 40 mmol / d in a subject of normal weight and having a balanced diet.
In the case of acidosis of extrarenal origin, the kidney will be able to multiply by five the excretion of H + by NH 4 + .Extrarenal acidosis is therefore accompanied by a significant increase in NH 4 +, which is greater than 80 mmol / d.NH 4 + is not routinely assayed by laboratories, but its renal excretion can be indirectly determined by urinary TrA analysis, as this cation is excreted with Cl – in the urine.
Normally, in the urine: (Na + + K + ) – Cl – > 0
In fact, it is mainly anions which are not assayed, such as sulphates, phosphates and organic anions.
The formula for precisely knowing the urinary NH 4 + is: NH 4 + = 82 – 0.8 (Na + + K + – Cl – )
In case of acidosis with a suitable renal response, the increase of NH 4 Cl will reverse the urinary TrA which becomes negative.
In the case of acidosis with an inadequate renal response (the kidney is wholly or partly responsible for acidosis), urinary TrA remains positive with an NH 4 Cl excretion of less than 80 mmol / d.
It has no interest in common practice in the etiological assessment of metabolic acidosis.
Indeed, the interpretation of urinary pH in the exploration of acidosis is made difficult for many reasons.
– First of all, it is necessary to make sure that there is no urine-like urine infection (such as Proteus), as the pH becomes alkaline due to bacterial ureolysis.
Since DHA is necessary for urine acidification, urinary pH can only be analyzed in a standing and relative hydric restriction.
– Urinary pH can only be interpreted if serum potassium is normal.
Indeed, we have seen that dyskalemias modify the renal availability of NH 3 . Hypokalemia increases the availability of NH 3 , allowing H + to be eliminated as NH 4 + , resulting in an “alkaline” urinary pH. Hyperkalaemia decreases the renal availability of NH 3 , which tends to favor the excretion of H + in free form, hence an “acidic” urinary pH.
Similarly, treatment with corticosteroids increases the renal availability of NH 3 .
INFLUENCE OF ACIDOSIS ON KALIEMY:
In the assessment of acidosis, serum potassium must be measured, as the latter is influenced by acid-base equilibrium. In acute mineral acidosis (distal tubular acidosis), serum potassium rises by K + outcome of the cell. This effect is not present in case of acute organic acidosis (lactic acidosis). On the other hand, chronic acidosis is often associated with hypokalaemia by renal leakage of K + .
Etiologies of metabolic acidosis:
The mechanisms involved in the occurrence of metabolic acidosis are four: acid overload, acid excretion deficiency, loss of bases and dilution acidosis.
The kidney’s ability to eliminate an acidic charge is limited despite the physiological increase in proton renal excretion as NH 4 Cl. In the event of acid overload, acidosis may develop despite the increase of urinary acid excretion.
Exogenous acid overload:
The etiologies are:
– the supply of NH 4 Cl, lysine hydrochloride or arginine, methionine sulfate.
Acidosis is hyperchloremic. There is often a blood osmotic hole, as shown by the difference between the osmolality measured by the cryoscopic delta and the calculated osmolality: (2 ‘ Na + ) + 10. This difference is explained by the presence of the toxicant or its metabolites in the plasma;
– intoxication (either accidental or suicidal) by methanol, acetylsalicylic acid, ethylene glycol and paraldehyde.
In all cases, a blood TrA is present, consisting of the toxic anion or its metabolites.
Ethylene glycol poisoning associates neurological disorders (pseudoethylism) with acute renal failure with the presence of a large number of crystals of calcium oxalate in the urine and in the renal parenchyma.
Methanol poisoning involves pseudoethylism, abdominal pain with vomiting, vision disorders such as retinal edema and papillitis.
Paraldehyde poisoning is observed in alcoholics and drug addicts. It combines abdominal pain, neurological signs, and hyperleukocytosis. The diagnosis is made by exclusion because no metabolite can be assayed.
Salicylate poisoning is associated with respiratory alkalosis which generates lactic acidosis. This explains, more than the presence of the salicylate anion, the TrA observed.
Endogenous acid overload:
This is the accumulation of lactic acid due to an imbalance between production and consumption of this acid.Production takes place in tissues without mitochondrial enzymes of the Krebs cycle, or in the case of anaerobic cell metabolism. Consumption takes place in the aerobic Krebs cycle and by hepatic and renal gluconeogenesis (Cori cycle). Normal lactacidaemia is 1 mmol / L.
We speak of lactic acidosis if the lactacidaemia is greater than 5 mmol / L. In general, the assay is not useful for diagnosis which is easily performed in the presence of severe acidosis (pH < 7.10 and HCO 3- < 10 mmol / L), with TrA in an evocative clinical context.
Biguanides (metformin: Glucophage t , Stagid t ) are very good antidiabetics, but their use is limited by the fact that they can block gluconeogenesis, and therefore generate lactic acidosis. They are contraindicated or must be stopped in the following cases:
– renal failure, hepatocellular insufficiency, cardiac or respiratory failure;
– situations at risk of acute renal failure, such as after injection of iodinated contrast agent or nephrotoxic molecules;
– all situations of “stress”: anesthesia, surgery, dehydration, infection …
Note the frequency of the entangled causes of lactic acidosis, such as a state of shock at the origin of tissue hypoxia generating lactate anions and complicating liver and renal insufficiency reducing their consumption.
· Diabetic ketoacidosis
Ketoacidosis is observed mainly in the diabetic type I patient with insulin deficiency. Insulin deficiency has an impact on adipose tissue and the liver. In adipose tissue, insulin deficiency activates the hormone-sensitive lipase, resulting in the release of large amounts of fatty acids. In the hepatocyte, insulin deficiency lowers the level of malonyl-coenzyme A (CoA), allowing the fatty acids to be metabolized in the mitochondria to acetyl-CoA and then to ketoacids. The keto acids consist of acetoacetic acid (which will be metabolized to acetone), and beta-hydroxybutyric acid. Only some of the keto acids will be used by the brain and kidney for energy purposes, hence their accumulation in the plasma.
Diabetic ketoacidosis associates neurological signs (confusion, even coma), with extracellular dehydration (secondary to hyperglycemia with glycosuria), and with an acetone odor of the breath. Biology revealed hyperglycaemia associated with blood ketone bodies (positive acetest in serum diluted eight fold) and urine, severe acidosis with a pH below 7.3 and HCO 3- less than 10 mmol / L, with TrA .
Initial transfer hyperkalemia regresses as a result of treatment. Sometimes there is no TrA because the kidney removes all ketone bodies if the insulin deficiency slowly settles.
· Other ketoacidoses
– Fasting ketoacidosis: decreased insulin secondary to fasting causes moderate acidosis.
– Alcoholic ketoacidosis: fasting, associated with the massive ingestion of alcohol, often aggravated by digestive disorders (vomiting and / or diarrhea), leads to major lipolysis, with formation of ketones. Biology is different from that of diabetic ketoacidosis because:
– there is no hyperglycemia or glycosuria;
– the acetest may be defeated because it recognizes only acetoacetic acid. In alcoholic ketoacidosis, the main anionic index is beta-hydroxybutyric acid;
– Chloremia may be low due to vomiting, with hypochloruria.
Bacterial proliferation in the gastrointestinal tract:
The bacteria of the digestive tract produce a large quantity of organic acids (D-lactic acid, butyric acid, lactic acid, etc.) which are metabolized into neutral products, thus without generating protons. H + can accumulate in the event of an overproduction of these acids due to bacterial growth, antibiotic treatment or inflow into the digestive tract of carbohydrates, or in the event of metabolic failure of the organic anions formed (hepatic or renal insufficiency).
LOSSES OF ALKALI:
Some digestive secretions are rich in HCO 3- , especially bile and pancreatic juice. HCO 3- is normally reabsorbed in the colon, which makes the fecal loss of HCO 3- negligible.
A digestive loss of alkalis can be observed in cases of acute or chronic diarrhea; pancreatic and biliary fistula;treatment with cholestyramine (Questran t ), CaCl 2 , MgSO 4 , the latter two drugs directly chelating HCO 3- .
Acidosis is free of blood TrA, as there is an increase in tubular reabsorption of Cl – due to extracellular dehydration.Urinary TrA is constantly negative. Hypokalaemia is often present, due to the digestive losses of K + , but also of an inadequate kaliuresis.
In the case of digestive loss of alkalis, urinary pH should be adjusted, ie acidic. But we have seen the difficulties of interpretation of the urinary pH in case of dyskalaemia and of hydration disorders.
DEFAULT OF EXERCISE OF THE DAILY ACID LOAD:
Chronic renal insufficiency is accompanied by acidosis with TrA due to the retention of phosphates, sulphates and other organic anions.
Acidosis is related to decreased excretion of H + as NH 4 + , which is parallel to the nephron reduction. We have seen that the synthesis of NH 4 + decreased due to the reduction in the energy requirements of the insufficient kidney.
Up to an advanced stage of nephron reduction, acidosis is compensated because acid retention is buffered by the alkaline salts of bone tissue, which would explain the demineralization of patients with renal insufficiency.
These are tubular dysfunctions, cause and pathophysiology, with or without moderate impairment of renal function.Biology shows hyperchloremic acidosis and urinary excretion of NH 4 + too low given acidosis (urinary positive TrA).
Tubular proximal (or type 2) acids:
It is characterized by a lowering of the reabsorption threshold for HCO 3- in the proximal tube at a variable level, between 16 and 20 mmol / L. Once the threshold is reached, HCO 3- is completely reabsorbed, and the entire process of urine acidification continues normally.
Blood tests show hypokalemia and signs of haemoconcentration. In the urine, the pH is adjusted accordingly; there is no HCO 3- . NH 4 + is in insufficient quantity.
Diagnosis is confirmed in specialized laboratories by reducing the ratio of the reabsorption capacity of HCO 3 – to the glomerular filtration rate (TmHCO 3 / DFG), which is less than 20 mmol / L.
Further signs of proximal tubular disease should be investigated: orthoglycaemic glycosuria, aminoaciduria, elevated phosphorus and uric acid clearance.
Distal tubular acidosis (or type 1):
Distal tubular acidosis (ATD) is of two types: hypokalemic ATD and hyperkalaemic ATD.
– ATD with hypokalaemia.
The origin is either a backscattering of the H + ions due to the inability of the distal tube to maintain an H + ion gradient between the tubular cells and the tubular lumen, or a decrease in the number or activity of the pumps H + ATPases of alpha intercalated cells.
The clinical picture associates a discrete extracellular dehydration and an osteopenia. Biology reveals hyperchloremic acidosis with hypokalaemia by secondary hyperaldosteronism, low citraturia and high calciuria. The urine pH is alkaline, with bicarbonatura, the excretion of NH 4 + is low.
– ATD with hyperkalemia.
The origin is either an alteration of voltage by loss of the secretion of H + ions in the collecting tube, or a hypoaldosteronism.
In the case of voltage alteration, biology reveals hyperkalemic hyperchloremic acidosis, low excretion of NH 4 + with contraction of extracellular volumes. Renin and aldosterone are elevated.
The biology is identical in hypoaldosteronism, but in a rather hyperhydrated patient, with a low aldosterone, while the renin is either high or low, depending on the etiology.
ACIDOSE OF DILUTION:
It is linked to the rapid administration of bicarbonate-free liquids, which leads to a reduction in the reabsorption of HCO 3- . In fact, the H + ion balance is normal.
Treatment of metabolic acidosis:
Treatment of metabolic acidosis is primarily the treatment of its cause. Symptomatic treatment is not always necessary.
MEANS OF TREATMENT:
There are three ways to correct metabolic acidosis: alkalinization, hyperventilation and extrarenal cleansing.
The most commonly used alkaline solution is NaHCO 3 . It is used either orally in a magisterial preparation (2 to 6 g / d), or in the form of Vichy water (of which 1 L brings 48 mmol of Na + and of HCO 3- ). The intravenous form exists in 1.4% solution (molar solution providing 165 mmol / L of Na + and HCO 3- ) or 4.2% (three times molar). The initial dosage is 1 to 2 mmol / kg by slow infusion, the rest of the treatment being adapted as a function of the pH correction.
– Na + molar lactate is practically no longer used, because in addition to the considerable Na + (1000 mmol / L Na +and lactate) it generates, it must be metabolized by the liver in HCO 3- . In severe acidosis that would warrant its use, such as lactic acidosis or ketoacidosis, hepatic metabolism is often disrupted.
– Trihydroxy-methylamino-methane (THAM) acetate can be used by venous route (despite the risk of venous thrombosis and tissue necrosis) or per os, as it sequesters the H + in the gastrointestinal tract. The dosage by venous route is calculated according to the formula:
– 0.3 ‘ basic deficit ‘ weight in kg
Half the dose is perfused in 10 minutes, the rest in 1 hour. The maximum dose is 15 mmol / kg / day.
– Tripotassium citrate is a magisterial preparation which allows a gentle alkalization, at the dosage of 1 g / 10 kg of weight / day.
This physiological compensation means allows for the elimination of CO 2 and therefore a decrease in the H +concentration.
Physiological hyperventilation must therefore always be respected.
In severe acidosis, mechanical ventilation may be used, but its efficacy has never been evaluated.
It helps to correct acidosis, without the risk of overloading or overcompensation. The different techniques are equivalent: hemodialysis, or haemodiafiltration, or continuous or intermittent hemofiltration. Its use requires a correct hemodynamic state and effective CO 2 elimination by ventilation. Preference will be given to the HCO 3- bath.
CONDUCT OF TREATMENT:
In acute acidosis, there is a risk of decreased myocardial contraction, cardiac arrhythmias and vasodilatation, which may result in shock. The prognosis depends more on the cause of acidosis than on the blood pH.
The treatment depends on the pH value.
If the pH is below 7.2, alkalinize either with 1.4% NaHCO 3 or with THAM acetate. The associated mechanical ventilation allows the elimination of CO 2 and the reduction of the energy expenditure thus of the production of H + .Extrarenal scrubbing can be used in cases of kidney failure, some poisoning or failure of alkalization.
If the pH is above 7.2, alkalization is not recommended, treatment of the cause would be sufficient. This is particularly true for lactic acidosis, ketoacidosis and poisoning.
In the case of chronic acidosis, the long-term risk is osteoporosis and increased protein catabolism.
Alkalization should be prescribed based on serum potassium. In the case of hyperkalemia, NaHCO 3 or perfumed THAM syrup are prescribed. In case of hypokalemia, tripotassium citrate should be used.
The sodium intake should be taken into account when using NaHCO 3 .
It should also be noted that the digestive tolerance of alkaline solutes per os is generally not good.