STUDY - Technical - New Dacian's Medicine
Acidosis
and Alkalosis (2)
Translation Draft
I will now move on to metabolic acidosis (which will be a fairly consistent post - in the idea that tomorrow I will make a maximum effort with alkalose and complete this group of posts as soon as possible).
Metabolic acidosis may occur due to increased production of endogenous acids (such as lactate and ketoacids), loss of bicarbonate (in diarrhea) or accumulation of endogenous acids (as in renal failure).
Metabolic acidosis has strong effects on the respiratory, cardiac and nervous systems. The decrease in blood pH is accompanied by a characteristic increase in ventilation, especially in the current volume (Kussmaul breath). Intrinsic cardiac contractility may be depressed, but inotropic function may be normal due to the release of catecholamines.
Both peripheral arterial vasodilation and central vasoconstriction may be present, with decreased central vascular and pulmonary compliance predadipleing in pulmonary edema, even if there is minimal volemic overload. The function of the central nervous system is depressed and headache, lethargy, stupor and in some cases even coma appear. Glucose intolerance may also occur.
It is generally accepted that the treatment of metabolic acidosis with alkaline solutions should be reserved for severe acidemia, unless the patient does not have "HCO3-potential" in plasma. HCO3- potential can be estimated from the growth of the anionic hole (GA). It should be determined whether plasma anionic acids are metabolizable (e.g. beta-hydroxybutyrate, acetoacetate, lactate) or non-metabolizable (anions that accumulate in chronic renal failure or ingestion of toxins).
The latter require the restoration of renal function to recover HCO3 deficiency, a slow and often unpredictable process. Subsequently, patients without GA (hyperchloremic acidosis and GA) or a GA attributed to non-metabolizable anions in the event of renal failure require either oral (NaHCO3 or Shohl) or intravenous (NaHCO3) in a quantity necessary to increase plasma slow lye to a level between 20 and 22 mmoli/l.
Existing controversies are regarding the use of alkalis in patients with pure GA acidosis caused by the accumulation of metabolizable organic anions (cetoacidosis or lactic acidosis). In general, severe acidosis (pH less than 7.2) requires intravenous administration of 50-100 mEq of NaHCO3 in 30-45 minutes within the first 1-2 hours of therapy. Such a modest amount of alkalis in this situation provides an additional safety measure, but it is essential to monitor plasma electrolytes during therapy, as K+ may decrease as the pH increases.
As we have previously presented, we are dealing with two large categories of clinical metabolic acidosis: 1. with high GA and 2. normal GA or hyperchloremic acidosis.
Acydoses with large anionic hole have four major main causes: 1. lactic acidosis, 2. ketoacidosis, 3. ingestion of toxins and 4. acute and chronic renal failure. The initial screening to differentiate acidosis with high GA should include: 1. a positive anamnesis of the ingestion of drugs and toxins, as well as the measurement of blood arterial gases to detect the coexistence of respiratory alkalosis (salicylates), 2. determination of the presence of diabetes mellitus (diabetic ketoacidosis), 3. looking for evidence of alcoholism or increased levels of beta-hydroxybutyrate (alcoholic ketoacidosis), 4. observation of clinical signs of uremia and determination of blood urea (US) and creatinine (uremic acidosis), 5. inspection of the urine summary for the highlighting of oxalate crystals (ethylene glycol), 6. recognition of the many clinical situations in which lactate levels can be increased (hypotension, shock, heart failure, leukemia, cancer and ingestion of drugs and toxins).
For lactic acidosis, the accumulation in plasma of L-lactate may be secondary to an obvious tissue hypoxia (type A) - circulatory failure (shock, heart failure), severe anaemia, cholera, mitochondrial enzyme defects and inhibitors (carbon monoxide, cyanides), or occult disorders (type B) such as hypoglycaemia (glycogen storage disease), seizures, diabetes mellitus, ethanol, liver failure, malignancy and salicylates, in which overproduction and/ or decreased liver metabolism of lactate may occur.
Unrecognized ischemia or intestinal infarction in a patient with severe atherosclerosis or cardiac decompensation and receiving vasopressors presents common causes of lactic acidosis. D-lactate acidosis, commonly associated with jejunoial bypass or intestinal obstruction due to stimulation of intestinal bacteria, can cause both an increase in GA and hyperchloremia.
From the point of view of treatment, the underlying conditions affecting the milk metabolism should be corrected first, tissue infusion having to be restored when a is inadequate. Vasoconstrictors should be avoided if possible because they worsen tissue infusion. Alkaline therapy is reserved for acute, severe acidemia (pH less than 7.1) in the idea of improving cardiac function and the use of lactate. However, NaHCO3 therapy can cause a paradoxical depression of cardiac function and an exacerbation of acidosis by increasing the production of lactate (HCO3- stimulates phosphofructochinase).
While the use of alkalis in moderate lactic acidosis is controversial, it is generally accepted that the attempt to restore pH or HCO3 to normal by taking NaHCO3 exogenous has negative effects. A reasonable attitude is to infuse a sufficient amount of NaHCO3 to increase the arterial pH no more than 7.2 in 30-40 minutes. NaHCO3 therapy can cause fluid overload and hypertension due to the fact that a large amount is required when the accumulation of lactic acid is continuous. The administration of fluids is poorly tolerated due to central venoconstriction, especially in oliguric patients. When the underlying causes of lactic acidosis can be remedied, the lactate in the blood will convert to HCO3- and cause an increased alkalosis.
Ketoacidosis has two main forms of manifestation: diabetic and alcoholic. In the case of diabetic ketoacidosis, the situation is determined by increased metabolism of fatty acids and accumulation of ketoacids (acetoacetate and beta-hydroxybutyrate). Diabetic ketoacidosis usually occurs in insulin-dependent diabetes mellitus in combination with stopping insulin administration or under conditions of intercurrent conditions such as infections, gastroenteritis, pancreatitis or myocardial infarction that increase insulin requirements, temporarily and acutely.
The accumulation of ketoacids participates in the increase of GA and is most commonly accompanied by hyperglycaemia (glycaemia greater than 17 mmoli/ l or 300 mg/ dl). It should be noted that because insulin prevents ketone production, bicarbonate therapy is rarely necessary, except for severe acidemia (pH of less than 7.1) and then only within certain limits (as previously discussed for the correction of lactic acidosis). In the case of alcoholic cetocidosis, chronic alcoholism can develop ketoacidosis when alcohol consumption is stopped suddenly (being frequently associated with vomiting, abdominal pain, starvation and volemic deplation).
The glucose concentration is low or normal and acidosis may be severe due to increased levels of ketones, predominantly beta-hydroxybutyrate. Moderate lactic acidosis may coexist due to alteration of the redox process. The reaction of nitroprusiat with ketones (Acetest) can detect ketoacid acid, but not beta-hydroxybutyrate, so the degree of ketone and ketonuria can be underestimated. Typically, insulin levels are low and the concentration of triglycerides, cortisol, glucagon and growth hormone are increased.
Treatment consists in the restoration of intravenous volume and administration of intravenous glucose (5% glucose in 0.9% NaCl). Hypophosphatemia, hypokalemia and hypomagnesemia may coexist and should be corrected. Hypophosphatemia is commonly observed 12-24 hours after admission and may be exaggerated by glucose administration and, if severe, may induce rhabdomyolysis. Upper digestive haemorrhage, pancreatitis and pneumonia may accompany this condition.
Drug-induced acidosis and toxins can have several causes. Intoxication with salicylates in adults causes metabolic acidosis with high GA, in which only a certain part of GA is given by salicylates. The production of lactic acid is also frequently increased, on the one hand as a direct effect of the drug, and on the other hand as a result of stimulation at the central level of the respiratory center due to salicylates causing a decrease in PaCO2 (respiratory alkalosis). Mixed acidobasic imbalances (metabolic acidosis concomitant with respiratory alkalose) given by salicylates are common in adults.
Treatment should be started with gastric lavage with isotone saline solution (not NaHCO3) and followed by the administration of activated charcoal. To facilitate the removal of salicylates, NaHCO3 is administered intravenously in adequate amounts to alkalize urine and maintain urinary flow (urinary pH greater than 7,5). While this form of therapy is simple in patients with acidosis, respiratory alkalosis can make this approach risky.
Acetazolamide may be given when alkaline diuresis cannot be achieved, but this medicine may cause systemic metabolic acidosis if NaHCO3 is not administered concurrently. Hypopotasemia, which may be severe, occurs as a result of alkaline diuresis given by NaHCO3 or acetazolamide or by respiratory alkalosis and should be treated promptly and aggressively. Glucose-containing fluids should be administered due to the danger of hypoglycaemia. Excessive insensitive fluid loss can cause severe volemic doutation and hypernatremia. If renal failure prevents rapid clearance of salicylates, hemodialysis should be performed even with a bicarbonate dialysis.
We're about to tackle alcohol-induced acidosis. In most physiological situations sodium, urea and glucose generate osmotic blood pressure. Calculated and determined plasma osmolarity must differ by less than 10-15 mmoli/ kg H2O. When the measured osmolarity exceeds that calculated by more than 15-20 mmoli/ kg H2O, we are dealing with one or two situations. Either osmotic sodium is falsely low, such as in the case of hyperlipidemia or hyperproteinemia (pseudohyponatremia), or other osmolites different from sodium, glucose or urea salts have accumulated in plasma.
Examples include mannitol, contrast substance, isopropyl alcohol, ethylene glycol, ethanol, methanol and acetone. In these situations, the difference between calculated and measured osmolarity (osmolar hole) is disproportionate to the concentration of unmeasured solvents. With adequate anamnesis and a high degree of suspicion, the identification of the osmolar hole is useful in identifying the presence of acidosis with GA caused by toxins.
Ingestion of ethylene glycol (commonly used as antifreeze) leads to metabolic acidosis and severe damage to the central nervous system, heart, lungs and kidneys. The increase in GA and osmolar hole is attributed to ethylene glycol and its metabolites, oxalic acid, glycolic acid and other organic acids. Lactic acid production increases secondary to inhibition of the tricarboxylic acid cycle and alteration of intracellular redox state. The diagnosis is relieved by the recognition of oxalate crystals in the urine.
From a treatment point of view, this includes the prompt establishment of saline or osmotic diuresis, supplemented with thiamine and pyridoxine, ethanol and dialysis. Intravenous ethanol is administered to a level of 22 mmoli/ l and helps to achieve lower toxicity, as it acts competitively with ethylene glycol within metabolism, via alcohol dehydrogenase and alters cellular redox status.
Ingestion of methanol (methyl alcohol) causes metabolic acidosis and its metabolites formaldehyde and formic acid cause severe damage to the optic nerve and central nervous system. Lactic acid, ketoacids and other unidentified organic acids may contribute to acidosis. Due to its small molecular weight, an osmolar hole is frequently present. The treatment is similar to that used in ethylene glycol poisoning including general supportive measures, ethanol administration and hemodialysis.
Hyperchloremic acidosis from moderate renal failure is eventually converted into high GA acidosis in advanced renal failure. Low filtration and reabsorption of organic anions contributes to pathogenesis. As kidney disease progresses, the number of functional nephrons becomes insufficient to cope with net acid production. Uremic acidosis is therefore characterized by a decrease in the production rate of NH4+, mainly due to a decrease in renal mass. HCO3- rarely descends below 15 mmoli/ l and GA rarely exceeds 20 mmol/l. Acid retention in chronic renal failure is buffered by alkaline salts in the bones.
Despite significant acid retention (more than 20 mmoli/day), serum HCO3-does not decrease further, indicating the participation of buffer systems outside the extracellular compartment. Chronic metabolic acidosis also increases urinary calcium excretion, in proportion to cumulative acid retention. Both uremic acidosis and hyperchloremic acidosis in renal failure require oral alkali treatment to maintain HCO3- between 20 and 24 mmoli/ l.
This can be done with a small amount of alkalis (1 to 1.5 mmoli/ kg body/ day). It is known that the administration of alkalis prevents the harmful effects of the H+ balance on the bones. Sodium citrate (Shohl solution) or NaHCO3 tablets are salts with an equal alkalinizing effect. Citrate increases the absorption of aluminum from the gastrointestinal tract and should never be administered together with antacids containing aluminum, due to the risk of aluminum poisoning. When hyperpotasemia is present, furosemide (60 - 80 mg/ day) is added.
I will now address hyperchloremic metabolic acidosis. Alkalis can be lost from the gastrointestinal tract into diarrhea or through the kidneys (in ATR). In these conditions, mutual exchanges of Cl- and HCO3- a normal GA is achieved. In pure hyperchloremic acidosis, the increase of Cl- above normal values equals the decrease of HCO3-. The absence of such a relationship suggests a mixed medical condition. Diarrhea causes the loss and decomposition of large amounts of HCO3-.
Because diarrheal stools contain higher amounts of HCO3- and HCO3- decomposed than plasma, metabolic acidosis develops at the same time as volemic deletion. Instead of an acidic urinary pH (as expected in a systemic acidosis), urinary pH is commonly around 6 due to the fact that metabolic acidosis and hyperpotasemia increase the synthesis and renal excretion of NH4+, thus providing a urinary buffer system that increases the pH of urine.
Metabolic acidosis caused by gastrointestinal loss associated with high urinary pH is differentiated from renal tubular acidosis (ATR), because urinary excretion of NH4+ is typically low in ATR and increased in diarrhea. Urinary levels of NH4+ can be estimated by calculating net urinary load (UN). UN is the difference between the amount of Na+ and K+ and the total of Cl-. When the UN is negative, the urinary ammonium levels (NH4+) are increased appropriately, suggesting an extrarenal cause of acidosis.
Apart from diarrhoea (HCO3- lost in the gastrointestinal tract), another extrarenal cause of hyperchloremic metabolic acidosis is parenteral hypernutrition with Cl-salts of essential amino acids and insufficient alkalis (acetate). However, if urinary NH4+ is low, the most likely cause is ATR. Caution should be taken in the case of ketonuria or the presence of medicinal anions in the urine, which cancel the estimated net negative load.
Loss of renal parenchyma through progressive renal disease leads to hyperchloremic acidosis when the glomerular filtration rate (GFG) is 20 and 50 ml/ min and uremic acidosis with high GA when RFG drops below 20 ml/ min. Such an evolution occurs constantly in tubulo-interstitial renal disorders, but hyperchloremic metabolic acidosis may also exist in advanced glomerulonephritis.
In advanced renal failure, ammoniogenesis is reduced in proportion to the loss of functional renal mass, and the accumulation of ammonium in the medullary collector tube may also be affected. Due to adaptive increases in K+ secretion in the collector duct and colon, acidosis from chronic renal failure is typical normopotasemic.
Most forms of proximal ATR (type 2 OF ATR) are caused by a generalized proximal tubular dysfunction with glycosuria, generalized amino aciduria and phosphaturia (Fanconi syndrome). Urine is adequately acidifyd (pH less than 5.5) and either a low plasma concentration of HCO3- or an increased fractional excretion of HCO3- (greater than 10-15%) is present. with an almost normal serum HCO3 (less than 20 mmoli/l). Large amounts of HCO3-exogenous are required in the proximal ATR, as HCO3- is not normally reabsorbed into the proximal tube causing increased renal potassium and hypopotasemia losses.
Classical distal ATR (type 1 ATR) typically includes hypokaliemia, hyperchloremic acidosis, low urinary excretion of NH4+ (positive net urine load) and inadequate urinary pH (greater than 5.5). these disorders suggest that one or both active proton pumps present in the collector duct (H+ - ATP-aza or H+, K+ - ATP-ase) are defective. In addition, the excretory rate of NH4+ is evenly lowered when the degree of systemic acidosis is taken into account, indicating that the kidney is responsible for metabolic acidosis.
Excretion of NH4+ is low due to insufficient retention of NH4+ in the medullary collector duct as a result of a higher than normal pH of tubular fluid in this segment, and urinary pH is higher as a result of decreased H+ secretion. In amphotericin B poisoning, distal ATR is given by the inability to maintain a pH gradient along the collector duct, while many other forms of distal ATR appear to be the result of deficiency in the operation of the H+ pump or an inadequate number of H+ pumps.
Distal ATR occurs frequently in association with a systemic condition such as Sjogren's syndrome or multiple myeloma and is called "secondary" distal ATR. But distal ATR can also appear as a hereditary condition not associated with a systemic disease. ATR in renal transplantation can be both proximal and distal, but chronic rejection is commonly associated with the distal type. Although hyperchloremic metabolic acidosis and hypopotasemia occur regularly in advanced renal failure, in type 4 ATR hypopotasemia is disproportionate to the decrease in RFG due to the coexistence of acidic and potassium secretion dysfunction. Urinary ammonium excretion is invariably low, and renal function may be compromised due to diabetic nephropathy, amyloidosis or tubulo-interstitial disorders.
In the case of treatment, chronic metabolic acidosis from classical distal ATR is frequently corrected by oral administration of a sufficient amount of alkalis to neutralize the production of metabolic acids in the diet. In adult patients with distal ATR, this amount is equal to 1-3 mmoli/ kg body/ day in the form of Shohl solution or NaHCO3 tablets. Correction of acidosis decreases potassium urinary excretion and thus resolves hypopotasemia and sodium depletion. So in most adult patients with distal ATR, potassium supplement is not necessary.
Now, a few things about hyporeninemic hypoaldosteronism. This typically causes hyperchloremic metabolic acidosis, commonly in elderly adults with diabetes mellitus or tubulo-interstitial impairment and renal failure. Patients consistently have mild to moderate renal failure and acidosis with increased serum C+ (5.3-6 mmoli/ l), associated hypertension and congestive heart failure. Both metabolic acidosis and hypopotasemia are far too high in relation to RFG impairment.
Nonsteroidal anti-inflammatory drugs may also cause hypopotasemia with hyperchloremic metabolic acidosis in patients with renal failure. In hyporenenemic hypoaldosteronism, the plasma activity of renin appears to be non-responsive to normal physiological stimuli, resulting in the secretion of aldosterone being low. Decrease dining Of K+ by taking cation-changing resins may increase renal ammoniogenesis and frequently improve or correct metabolic acidosis and hyperpotasemia.
Replacing mineralocorticoid with fluorocortisone also improves net acid excretion, but is contraindicated under conditions of coexisting hypertension or congestive heart failure. The combination of hyperchloremic metabolic acidosis, hyperpotasemia, hypertension, undetectable plasma renin activity and low aldosterone levels is known as type II pseudohypoaldosteronism. This condition is usually not associated with glomerular or tubulo-interstitial disease. Acidosis is moderate and can be given by hyperpotasemia.
Renin and aldosterone levels increase if volemic expansion is corrected by diuretics or salt restriction. Potassium excretion responds to sodium sulphate administration. Resistance to mineralocorticoid, along with loss of salt can cause hyperpotasemic hyperpotasemic acidosis hyperchloremic due to decreased efficiency of mineralocorticoid in the cortical collector tube.
Pseudohipoaldosteronism may occur in association with systemic lupus erythematosus, obstructive neuropathies, sickle cell anemia, drug-induced interstitial nephritis, cyclosporin therapy or rejection of renal transplantation.
Treatment of patients with metabolic acidosis and hyperpotasemia in chronic renal failure is not always necessary, and the decision to start this treatment is often based on the severity of hyperpotasemia. The decrease in K+ in serum often improves metabolic acidosis. Patients with hyporenenemic hypoaldosteronism may respond to the administration of cation-changing resins (sodium polystyrene sulfonate), alkali therapy or anse diuretics.
Volemic deletation should be avoided unless the patient experiences exaggerated volemic expansion or hypertension. Doses of mineralocorticoids that exceed physiological ones may be necessary, but they should be administered in combination with a coil diuretic to avoid excessive volume expansion and worsening of hypertension and to increase potassium excretion. Patients with pseudohypoaldosteronism type II require thiazid diuretics associated with salt restrictions.
I've been able to complete this post, after more than two "to three" days of toil... Thank you Holy Spirit!
I will now move on to metabolic acidosis (which will be a fairly consistent post - in the idea that tomorrow I will make a maximum effort with alkalose and complete this group of posts as soon as possible).
Metabolic acidosis may occur due to increased production of endogenous acids (such as lactate and ketoacids), loss of bicarbonate (in diarrhea) or accumulation of endogenous acids (as in renal failure).
Metabolic acidosis has strong effects on the respiratory, cardiac and nervous systems. The decrease in blood pH is accompanied by a characteristic increase in ventilation, especially in the current volume (Kussmaul breath). Intrinsic cardiac contractility may be depressed, but inotropic function may be normal due to the release of catecholamines.
Both peripheral arterial vasodilation and central vasoconstriction may be present, with decreased central vascular and pulmonary compliance predadipleing in pulmonary edema, even if there is minimal volemic overload. The function of the central nervous system is depressed and headache, lethargy, stupor and in some cases even coma appear. Glucose intolerance may also occur.
It is generally accepted that the treatment of metabolic acidosis with alkaline solutions should be reserved for severe acidemia, unless the patient does not have "HCO3-potential" in plasma. HCO3- potential can be estimated from the growth of the anionic hole (GA). It should be determined whether plasma anionic acids are metabolizable (e.g. beta-hydroxybutyrate, acetoacetate, lactate) or non-metabolizable (anions that accumulate in chronic renal failure or ingestion of toxins).
The latter require the restoration of renal function to recover HCO3 deficiency, a slow and often unpredictable process. Subsequently, patients without GA (hyperchloremic acidosis and GA) or a GA attributed to non-metabolizable anions in the event of renal failure require either oral (NaHCO3 or Shohl) or intravenous (NaHCO3) in a quantity necessary to increase plasma slow lye to a level between 20 and 22 mmoli/l.
Existing controversies are regarding the use of alkalis in patients with pure GA acidosis caused by the accumulation of metabolizable organic anions (cetoacidosis or lactic acidosis). In general, severe acidosis (pH less than 7.2) requires intravenous administration of 50-100 mEq of NaHCO3 in 30-45 minutes within the first 1-2 hours of therapy. Such a modest amount of alkalis in this situation provides an additional safety measure, but it is essential to monitor plasma electrolytes during therapy, as K+ may decrease as the pH increases.
As we have previously presented, we are dealing with two large categories of clinical metabolic acidosis: 1. with high GA and 2. normal GA or hyperchloremic acidosis.
Acydoses with large anionic hole have four major main causes: 1. lactic acidosis, 2. ketoacidosis, 3. ingestion of toxins and 4. acute and chronic renal failure. The initial screening to differentiate acidosis with high GA should include: 1. a positive anamnesis of the ingestion of drugs and toxins, as well as the measurement of blood arterial gases to detect the coexistence of respiratory alkalosis (salicylates), 2. determination of the presence of diabetes mellitus (diabetic ketoacidosis), 3. looking for evidence of alcoholism or increased levels of beta-hydroxybutyrate (alcoholic ketoacidosis), 4. observation of clinical signs of uremia and determination of blood urea (US) and creatinine (uremic acidosis), 5. inspection of the urine summary for the highlighting of oxalate crystals (ethylene glycol), 6. recognition of the many clinical situations in which lactate levels can be increased (hypotension, shock, heart failure, leukemia, cancer and ingestion of drugs and toxins).
For lactic acidosis, the accumulation in plasma of L-lactate may be secondary to an obvious tissue hypoxia (type A) - circulatory failure (shock, heart failure), severe anaemia, cholera, mitochondrial enzyme defects and inhibitors (carbon monoxide, cyanides), or occult disorders (type B) such as hypoglycaemia (glycogen storage disease), seizures, diabetes mellitus, ethanol, liver failure, malignancy and salicylates, in which overproduction and/ or decreased liver metabolism of lactate may occur.
Unrecognized ischemia or intestinal infarction in a patient with severe atherosclerosis or cardiac decompensation and receiving vasopressors presents common causes of lactic acidosis. D-lactate acidosis, commonly associated with jejunoial bypass or intestinal obstruction due to stimulation of intestinal bacteria, can cause both an increase in GA and hyperchloremia.
From the point of view of treatment, the underlying conditions affecting the milk metabolism should be corrected first, tissue infusion having to be restored when a is inadequate. Vasoconstrictors should be avoided if possible because they worsen tissue infusion. Alkaline therapy is reserved for acute, severe acidemia (pH less than 7.1) in the idea of improving cardiac function and the use of lactate. However, NaHCO3 therapy can cause a paradoxical depression of cardiac function and an exacerbation of acidosis by increasing the production of lactate (HCO3- stimulates phosphofructochinase).
While the use of alkalis in moderate lactic acidosis is controversial, it is generally accepted that the attempt to restore pH or HCO3 to normal by taking NaHCO3 exogenous has negative effects. A reasonable attitude is to infuse a sufficient amount of NaHCO3 to increase the arterial pH no more than 7.2 in 30-40 minutes. NaHCO3 therapy can cause fluid overload and hypertension due to the fact that a large amount is required when the accumulation of lactic acid is continuous. The administration of fluids is poorly tolerated due to central venoconstriction, especially in oliguric patients. When the underlying causes of lactic acidosis can be remedied, the lactate in the blood will convert to HCO3- and cause an increased alkalosis.
Ketoacidosis has two main forms of manifestation: diabetic and alcoholic. In the case of diabetic ketoacidosis, the situation is determined by increased metabolism of fatty acids and accumulation of ketoacids (acetoacetate and beta-hydroxybutyrate). Diabetic ketoacidosis usually occurs in insulin-dependent diabetes mellitus in combination with stopping insulin administration or under conditions of intercurrent conditions such as infections, gastroenteritis, pancreatitis or myocardial infarction that increase insulin requirements, temporarily and acutely.
The accumulation of ketoacids participates in the increase of GA and is most commonly accompanied by hyperglycaemia (glycaemia greater than 17 mmoli/ l or 300 mg/ dl). It should be noted that because insulin prevents ketone production, bicarbonate therapy is rarely necessary, except for severe acidemia (pH of less than 7.1) and then only within certain limits (as previously discussed for the correction of lactic acidosis). In the case of alcoholic cetocidosis, chronic alcoholism can develop ketoacidosis when alcohol consumption is stopped suddenly (being frequently associated with vomiting, abdominal pain, starvation and volemic deplation).
The glucose concentration is low or normal and acidosis may be severe due to increased levels of ketones, predominantly beta-hydroxybutyrate. Moderate lactic acidosis may coexist due to alteration of the redox process. The reaction of nitroprusiat with ketones (Acetest) can detect ketoacid acid, but not beta-hydroxybutyrate, so the degree of ketone and ketonuria can be underestimated. Typically, insulin levels are low and the concentration of triglycerides, cortisol, glucagon and growth hormone are increased.
Treatment consists in the restoration of intravenous volume and administration of intravenous glucose (5% glucose in 0.9% NaCl). Hypophosphatemia, hypokalemia and hypomagnesemia may coexist and should be corrected. Hypophosphatemia is commonly observed 12-24 hours after admission and may be exaggerated by glucose administration and, if severe, may induce rhabdomyolysis. Upper digestive haemorrhage, pancreatitis and pneumonia may accompany this condition.
Drug-induced acidosis and toxins can have several causes. Intoxication with salicylates in adults causes metabolic acidosis with high GA, in which only a certain part of GA is given by salicylates. The production of lactic acid is also frequently increased, on the one hand as a direct effect of the drug, and on the other hand as a result of stimulation at the central level of the respiratory center due to salicylates causing a decrease in PaCO2 (respiratory alkalosis). Mixed acidobasic imbalances (metabolic acidosis concomitant with respiratory alkalose) given by salicylates are common in adults.
Treatment should be started with gastric lavage with isotone saline solution (not NaHCO3) and followed by the administration of activated charcoal. To facilitate the removal of salicylates, NaHCO3 is administered intravenously in adequate amounts to alkalize urine and maintain urinary flow (urinary pH greater than 7,5). While this form of therapy is simple in patients with acidosis, respiratory alkalosis can make this approach risky.
Acetazolamide may be given when alkaline diuresis cannot be achieved, but this medicine may cause systemic metabolic acidosis if NaHCO3 is not administered concurrently. Hypopotasemia, which may be severe, occurs as a result of alkaline diuresis given by NaHCO3 or acetazolamide or by respiratory alkalosis and should be treated promptly and aggressively. Glucose-containing fluids should be administered due to the danger of hypoglycaemia. Excessive insensitive fluid loss can cause severe volemic doutation and hypernatremia. If renal failure prevents rapid clearance of salicylates, hemodialysis should be performed even with a bicarbonate dialysis.
We're about to tackle alcohol-induced acidosis. In most physiological situations sodium, urea and glucose generate osmotic blood pressure. Calculated and determined plasma osmolarity must differ by less than 10-15 mmoli/ kg H2O. When the measured osmolarity exceeds that calculated by more than 15-20 mmoli/ kg H2O, we are dealing with one or two situations. Either osmotic sodium is falsely low, such as in the case of hyperlipidemia or hyperproteinemia (pseudohyponatremia), or other osmolites different from sodium, glucose or urea salts have accumulated in plasma.
Examples include mannitol, contrast substance, isopropyl alcohol, ethylene glycol, ethanol, methanol and acetone. In these situations, the difference between calculated and measured osmolarity (osmolar hole) is disproportionate to the concentration of unmeasured solvents. With adequate anamnesis and a high degree of suspicion, the identification of the osmolar hole is useful in identifying the presence of acidosis with GA caused by toxins.
Ingestion of ethylene glycol (commonly used as antifreeze) leads to metabolic acidosis and severe damage to the central nervous system, heart, lungs and kidneys. The increase in GA and osmolar hole is attributed to ethylene glycol and its metabolites, oxalic acid, glycolic acid and other organic acids. Lactic acid production increases secondary to inhibition of the tricarboxylic acid cycle and alteration of intracellular redox state. The diagnosis is relieved by the recognition of oxalate crystals in the urine.
From a treatment point of view, this includes the prompt establishment of saline or osmotic diuresis, supplemented with thiamine and pyridoxine, ethanol and dialysis. Intravenous ethanol is administered to a level of 22 mmoli/ l and helps to achieve lower toxicity, as it acts competitively with ethylene glycol within metabolism, via alcohol dehydrogenase and alters cellular redox status.
Ingestion of methanol (methyl alcohol) causes metabolic acidosis and its metabolites formaldehyde and formic acid cause severe damage to the optic nerve and central nervous system. Lactic acid, ketoacids and other unidentified organic acids may contribute to acidosis. Due to its small molecular weight, an osmolar hole is frequently present. The treatment is similar to that used in ethylene glycol poisoning including general supportive measures, ethanol administration and hemodialysis.
Hyperchloremic acidosis from moderate renal failure is eventually converted into high GA acidosis in advanced renal failure. Low filtration and reabsorption of organic anions contributes to pathogenesis. As kidney disease progresses, the number of functional nephrons becomes insufficient to cope with net acid production. Uremic acidosis is therefore characterized by a decrease in the production rate of NH4+, mainly due to a decrease in renal mass. HCO3- rarely descends below 15 mmoli/ l and GA rarely exceeds 20 mmol/l. Acid retention in chronic renal failure is buffered by alkaline salts in the bones.
Despite significant acid retention (more than 20 mmoli/day), serum HCO3-does not decrease further, indicating the participation of buffer systems outside the extracellular compartment. Chronic metabolic acidosis also increases urinary calcium excretion, in proportion to cumulative acid retention. Both uremic acidosis and hyperchloremic acidosis in renal failure require oral alkali treatment to maintain HCO3- between 20 and 24 mmoli/ l.
This can be done with a small amount of alkalis (1 to 1.5 mmoli/ kg body/ day). It is known that the administration of alkalis prevents the harmful effects of the H+ balance on the bones. Sodium citrate (Shohl solution) or NaHCO3 tablets are salts with an equal alkalinizing effect. Citrate increases the absorption of aluminum from the gastrointestinal tract and should never be administered together with antacids containing aluminum, due to the risk of aluminum poisoning. When hyperpotasemia is present, furosemide (60 - 80 mg/ day) is added.
I will now address hyperchloremic metabolic acidosis. Alkalis can be lost from the gastrointestinal tract into diarrhea or through the kidneys (in ATR). In these conditions, mutual exchanges of Cl- and HCO3- a normal GA is achieved. In pure hyperchloremic acidosis, the increase of Cl- above normal values equals the decrease of HCO3-. The absence of such a relationship suggests a mixed medical condition. Diarrhea causes the loss and decomposition of large amounts of HCO3-.
Because diarrheal stools contain higher amounts of HCO3- and HCO3- decomposed than plasma, metabolic acidosis develops at the same time as volemic deletion. Instead of an acidic urinary pH (as expected in a systemic acidosis), urinary pH is commonly around 6 due to the fact that metabolic acidosis and hyperpotasemia increase the synthesis and renal excretion of NH4+, thus providing a urinary buffer system that increases the pH of urine.
Metabolic acidosis caused by gastrointestinal loss associated with high urinary pH is differentiated from renal tubular acidosis (ATR), because urinary excretion of NH4+ is typically low in ATR and increased in diarrhea. Urinary levels of NH4+ can be estimated by calculating net urinary load (UN). UN is the difference between the amount of Na+ and K+ and the total of Cl-. When the UN is negative, the urinary ammonium levels (NH4+) are increased appropriately, suggesting an extrarenal cause of acidosis.
Apart from diarrhoea (HCO3- lost in the gastrointestinal tract), another extrarenal cause of hyperchloremic metabolic acidosis is parenteral hypernutrition with Cl-salts of essential amino acids and insufficient alkalis (acetate). However, if urinary NH4+ is low, the most likely cause is ATR. Caution should be taken in the case of ketonuria or the presence of medicinal anions in the urine, which cancel the estimated net negative load.
Loss of renal parenchyma through progressive renal disease leads to hyperchloremic acidosis when the glomerular filtration rate (GFG) is 20 and 50 ml/ min and uremic acidosis with high GA when RFG drops below 20 ml/ min. Such an evolution occurs constantly in tubulo-interstitial renal disorders, but hyperchloremic metabolic acidosis may also exist in advanced glomerulonephritis.
In advanced renal failure, ammoniogenesis is reduced in proportion to the loss of functional renal mass, and the accumulation of ammonium in the medullary collector tube may also be affected. Due to adaptive increases in K+ secretion in the collector duct and colon, acidosis from chronic renal failure is typical normopotasemic.
Most forms of proximal ATR (type 2 OF ATR) are caused by a generalized proximal tubular dysfunction with glycosuria, generalized amino aciduria and phosphaturia (Fanconi syndrome). Urine is adequately acidifyd (pH less than 5.5) and either a low plasma concentration of HCO3- or an increased fractional excretion of HCO3- (greater than 10-15%) is present. with an almost normal serum HCO3 (less than 20 mmoli/l). Large amounts of HCO3-exogenous are required in the proximal ATR, as HCO3- is not normally reabsorbed into the proximal tube causing increased renal potassium and hypopotasemia losses.
Classical distal ATR (type 1 ATR) typically includes hypokaliemia, hyperchloremic acidosis, low urinary excretion of NH4+ (positive net urine load) and inadequate urinary pH (greater than 5.5). these disorders suggest that one or both active proton pumps present in the collector duct (H+ - ATP-aza or H+, K+ - ATP-ase) are defective. In addition, the excretory rate of NH4+ is evenly lowered when the degree of systemic acidosis is taken into account, indicating that the kidney is responsible for metabolic acidosis.
Excretion of NH4+ is low due to insufficient retention of NH4+ in the medullary collector duct as a result of a higher than normal pH of tubular fluid in this segment, and urinary pH is higher as a result of decreased H+ secretion. In amphotericin B poisoning, distal ATR is given by the inability to maintain a pH gradient along the collector duct, while many other forms of distal ATR appear to be the result of deficiency in the operation of the H+ pump or an inadequate number of H+ pumps.
Distal ATR occurs frequently in association with a systemic condition such as Sjogren's syndrome or multiple myeloma and is called "secondary" distal ATR. But distal ATR can also appear as a hereditary condition not associated with a systemic disease. ATR in renal transplantation can be both proximal and distal, but chronic rejection is commonly associated with the distal type. Although hyperchloremic metabolic acidosis and hypopotasemia occur regularly in advanced renal failure, in type 4 ATR hypopotasemia is disproportionate to the decrease in RFG due to the coexistence of acidic and potassium secretion dysfunction. Urinary ammonium excretion is invariably low, and renal function may be compromised due to diabetic nephropathy, amyloidosis or tubulo-interstitial disorders.
In the case of treatment, chronic metabolic acidosis from classical distal ATR is frequently corrected by oral administration of a sufficient amount of alkalis to neutralize the production of metabolic acids in the diet. In adult patients with distal ATR, this amount is equal to 1-3 mmoli/ kg body/ day in the form of Shohl solution or NaHCO3 tablets. Correction of acidosis decreases potassium urinary excretion and thus resolves hypopotasemia and sodium depletion. So in most adult patients with distal ATR, potassium supplement is not necessary.
Now, a few things about hyporeninemic hypoaldosteronism. This typically causes hyperchloremic metabolic acidosis, commonly in elderly adults with diabetes mellitus or tubulo-interstitial impairment and renal failure. Patients consistently have mild to moderate renal failure and acidosis with increased serum C+ (5.3-6 mmoli/ l), associated hypertension and congestive heart failure. Both metabolic acidosis and hypopotasemia are far too high in relation to RFG impairment.
Nonsteroidal anti-inflammatory drugs may also cause hypopotasemia with hyperchloremic metabolic acidosis in patients with renal failure. In hyporenenemic hypoaldosteronism, the plasma activity of renin appears to be non-responsive to normal physiological stimuli, resulting in the secretion of aldosterone being low. Decrease dining Of K+ by taking cation-changing resins may increase renal ammoniogenesis and frequently improve or correct metabolic acidosis and hyperpotasemia.
Replacing mineralocorticoid with fluorocortisone also improves net acid excretion, but is contraindicated under conditions of coexisting hypertension or congestive heart failure. The combination of hyperchloremic metabolic acidosis, hyperpotasemia, hypertension, undetectable plasma renin activity and low aldosterone levels is known as type II pseudohypoaldosteronism. This condition is usually not associated with glomerular or tubulo-interstitial disease. Acidosis is moderate and can be given by hyperpotasemia.
Renin and aldosterone levels increase if volemic expansion is corrected by diuretics or salt restriction. Potassium excretion responds to sodium sulphate administration. Resistance to mineralocorticoid, along with loss of salt can cause hyperpotasemic hyperpotasemic acidosis hyperchloremic due to decreased efficiency of mineralocorticoid in the cortical collector tube.
Pseudohipoaldosteronism may occur in association with systemic lupus erythematosus, obstructive neuropathies, sickle cell anemia, drug-induced interstitial nephritis, cyclosporin therapy or rejection of renal transplantation.
Treatment of patients with metabolic acidosis and hyperpotasemia in chronic renal failure is not always necessary, and the decision to start this treatment is often based on the severity of hyperpotasemia. The decrease in K+ in serum often improves metabolic acidosis. Patients with hyporenenemic hypoaldosteronism may respond to the administration of cation-changing resins (sodium polystyrene sulfonate), alkali therapy or anse diuretics.
Volemic deletation should be avoided unless the patient experiences exaggerated volemic expansion or hypertension. Doses of mineralocorticoids that exceed physiological ones may be necessary, but they should be administered in combination with a coil diuretic to avoid excessive volume expansion and worsening of hypertension and to increase potassium excretion. Patients with pseudohypoaldosteronism type II require thiazid diuretics associated with salt restrictions.
I've been able to complete this post, after more than two "to three" days of toil... Thank you Holy Spirit!
Have a week full of
achievements, understanding, love and gratitude!
Dorin, Merticaru