Buffers metabolic acidosis

The blood pH may return to normal in adults with mild overdoses. However, the blood pH can drop too far in children or more severely poisoned adults, resulting in metabolic acidosis. A lower buffering capacity or plasma protein-binding capacity may underlie the increased susceptibility to acidosis in children. Excretion of bicarbonate also means the bicarbonate in the blood is lower, and hence, there is an increased likelihood of metabolic acidosis. 

Tin metabolic acidosis (p. 652) there is an increase in glutamine processing by the kidneys. Not all the excess NH4 thus produced is released into the bloodstream or converted to urea some is excreted directly into the urine. In the kidney, the NH% forms salts with metabolic acids, facilitating their removal in the urine. Bicarbonate produced by the decarboxylation of a-lcetoglutarate in the citric acid cycle can also serve as a buffer in blood plasma. Taken together, these effects of glutamine metabolism in the kidney tend to counteract acidosis. ... 

Metabolic acidosis involves a build-up of hydrogen ions in the blood, thus lowering blood pH. Under normal physiological conditions, the kidneys excrete excess hydrogen ions, and release more bicarbonate ions into the bloodstream to buffer the excess acid. However, in renal failure, or in diabetic ketoacidosis, this mechanism either fails, or is unable to compensate to an adequate extent. Hence, metabolic acidosis is usually treated with sodium bicarbonate, either intravenously (1.26% or 8.4% i.v. solution) or orally (typically 1 g three times a day). Sodium bicarbonate 1.26% intravenous solution is isotonic with plasma (and with sodium chloride 0.9%), so may be given in large volumes (1-2 L) by peripheral venous catheter to correct metabolic acidosis and provide fluid replacement at the same time. Sodium bicarbonate 8.4% may only be given by central venous catheter. 

Q7 Ketoacidosis is a serious complication of diabetes mellitus. Because of insulin deficiency and consequent increased availability of fatty acids to the liver, the liver overproduces alpha-hydroxybutyrate and acetoacetic acid, increasing ketone production. The ketones are released into the circulation. They are strongly acidic and, when not effectively buffered, cause metabolic acidosis. Coma may then occur because of severe depression of the nervous system. 

In early cardiac arrest, adequate alveolar ventilation is the primary means of limiting carbon dioxide accumulation and controlling the acid base imbalance. With arrests of long duration, buffer therapy is often necessary. Sodium bicarbonate administration for cardiac arrest is controversial because there are few clinical data supporting its use, and it may have some detrimental effects. Sodium bicarbonate can be used in special circumstances (i.e., underlying metabolic acidosis, hyperkalemia, salicylate overdose, or tricychc antidepressant overdose). The dosage should be guided by laboratory analysis if possible. 

Sodium acetate is used as a buffering agent in various intramuscular, intravenous, topical, ophthalmic, nasal, oral, otic, and subcutaneous formulations. It may be used to reduce the bitterness of oral pharmaceuticals. It can be used to enhance the antimicrobial properties of formulations it has been shown to inhibit the growth of S. aureus and E. coli, but not C. albicans in protein hydrolysate solutions. It is widely used in the food industry as a preservative. Sodium acetate has also been used therapeutically for the treatment of metabolic acidosis in premature infants, and in hemodialysis solutions. ... 

Bjerneroth G, Sammeli 0, Li Y-C et al 1994 Effects of alkaline buffers on cytoplasmic pH in lymphocytes. Critical Care Medicine 22 1550-1556 Boilaert P E, Levy B, Nace L et al 1995 Hemodynamic and metabolic effects of rapid correction of hypophosphatemia in patients with septic shock. Chest 107 1698-1701 Bonagura J D, Reef V B 1998 Cardiovascular diseases. In Reed S M, Bayly W M (eds) Equine internal medicine. Saunders, Philadelphia, PA, pp. 290-370 Bonventre J V, Cheung J Y 1985 Effects of metabolic acidosis on viability of cells exposed to anoxia. 

Li Y-C, Wiklund L, Bjerneroth G 1997 Influence of alkaline buffers on cytoplasmic pH in myocardial cells exposed to hypoxia. Resuscitation 34 71-77 Lloyd M H, lies R A, Simpson B R et al 1973 The effect of simulated metabolic acidosis on intracellular pH and... 

Hypoventilation causes retention of C02 by the lungs, which can lead to a respiratory acidosis. Hyperventilation can cause a respiratory alkalosis. Metabolic acidosis can result from accumulation of metabolic acids (lactic acid or the ketone bodies p-hydroxybutyric acid and acetoacetic acid), or ingestion of acids or compounds that are metabolized to acids (methanol, ethylene glycol). Metabolic alkalosis is due to increased HC03, which is accompanied by an increased pH. Acid-base disturbances lead to compensatory responses that attempt to restore normal pH. For example, a metabolic acidosis causes hyperventilation and the release of C02, which tends to lower the pH. During metabolic acidosis, the kidneys excrete NH4+, which contains H+ buffered by ammonia. 

Adults and older children tend to correct the disturbance at this point. Young children, however, quickly develop a fall in the blood pH (metabolic acidosis), due to salicylate stimulation of metabolism. The toxic effects of salicylate and the loss of buffer base interfere with metabolic processes, and ketosis develops. Because the respiratory alkalosis and metabolic acidosis occur simultaneously, a child may present with a mixed disturbance and a relatively normal pH, or with frank acidosis. The PC02 will be lower than expected. Children < 4 yr develop metabolic acidosis more rapidly, without concurrent respiratory alkalosis. Dehydrationj is a serious problem because of insensible water loss and increased renal water loss (from an increased urine solute load). Severe losses of sodium and potassium are not uncommon (15). 

Metabolic acidosis is readily detected by decreased plasma bicarbonate (or a negative extracellular base excess), the primary perturbation in this acid-base disorder. Bicarbonate is lost in the buffering of excess acid. Causes include the foUowing ... 

The phosphate buffer system consists of serum inorganic phosphate (3.5 to 5 mg/dL), intracellular organic phosphate, and calcium phosphate in bone. Extracellular phosphate is present only in low concentrations, so its usefulness as a buffer is limited however, as an intracellular buffer, phosphate is more useful. Calcium phosphate in bone is relatively inaccessible as a buffer, but prolonged metabolic acidosis will result in the release of phosphate from bone. 

In mixed respiratory and metabolic acidosis, there is a failure of compensation. The respiratory disorder prevents the compensatory decrease in PaC02 expected in the defense against metabolic acidosis. The metabolic disorder prevents the buffering and renal mechanisms from raising the bicarbonate concentration as expected in the defense against respiratory acidosis. In the absence of compensatory mechanisms, the pH decreases markedly. 

In the conditions discussed above (diabetic ketoacidosis, lactic acidosis, uremia, and ingestion of salicylate, ethylene glycol, or methanol) metabolic acidosis is associated with an increased anion gap. In the face of excess metabolic acids, bicarbonate is depleted in the process of buffering excess hydrogen ions. Provided that the renal functions is normal, the kidney attempts to compensate by secreting an acid urine and retaining bicarbonate. 

Fig. 42.6. Renal glutamine metabolism. Renal tubule cells preferentially oxidize glutamine. During metabolic acidosis, it is the major fuel for the kidney. Conversion of glutamine to a-ketoglutarate generates NH4. Ammonium ion excretion helps to buffer systemic acidemia.

Ans. Metabolic acidosis is a lowering of the blood pH as a result of a metabolic disorder as opposed to the failure of the H2CO3 — HCO3 buffer system. For example, there is a large and serious decrease in pH as a result of uncontrolled diabetes. The blood pH may fall from the normal 7.4 to as low as 6.8. The increased H concentration is due to the large amounts of ketone bodies produced in the liver. The products are acetoacetic acid and -hydroxybutyric acid. The bicarbonate buffer system attempts to compensate for the excess H", and the excess CO2 must be eliminated at the lungs. However, so much COj is lost by ventilation that the absolute concentration of the buffer system decreases, so the capacity of the buffer system is severely compromised and cannot reduce the metabolically produced excess H". In such cases, clinical treatment involves the intravenous administration of sodium bicarbonate to restore buffer capacity. 

Base excess is a calculated value representing the amount of buffering anions in the blood (primarily HCO3 but also hemoglobin, proteins, phosphates, and others). The normal range of base excess is 2 mEq/L. A negative base excess (-3 mEq/L or less) indicates a deficit of base and a metabolic acidosis (i.e., ketoacidosis or lactic acidosis). A positive base excess (3 mEq/L or more) indicates metabolic alkalosis (may be present in compensation for a respiratory acidosis). 4... 

Additionally, hypoxia results in anaerobic metabohsm in tissues with a resulting lactic acidosis. While respirations normally are increased to buffer the metabolic acidosis, damage to the lungs reduces or removes this mechanism from availabihty. 

Chronic pulmonary failure may be further complicated by metabolic disturbances tending to metabolic alkalosis or metabolic acidosis. The mechanism leading to alkalosis is not always clear, but among the factors that may influence it are the loss of hydrogen and Cl ions, because of vomiting or because of selective Cl and potassium depletion as a result of undernourishment, and prolonged treatment with diuretics. It is usually assumed that severe respiratory acidosis is always accompanied by metabolic acidosis. This reasoning is based on the fact that when the same CO2 tensions are achieved in the blood in vivo and in vitro,the plasma concentration of bicarbonate for identical pH s is lower in vivo than in vitro. In reality, this bicarbonate deficit seems to result because (I) the buffer curve of the blood CO2 has a lower slope in vivo than in vitro and (2) hyperventilation in vivo leads to lactic acid accumulation in he blood. 

TRIS is one of the most common buffers used in the biology/biochemistry labs. It is used as alternative to sodium bicarbonate in the treatment of metabolic acidosis. It is also an emulsifying agent and absorbent for acidic gases, alkalizer and osmotic diuretic. 

Equation (3-13) shows that the equilibrium pH of the bicarbonate buffer system of plasma can be to some extent controlled by varying the partial pressure of carbon dioxide in the air to which the blood is exposed (i.e. in the lungs). Reduction in partial pressure results in carbon dioxide leaving the blood with a rise in the last term of Equation (3-13) provided that the bicarbonate concentration remains constant. The equilibrium pH of the buffer system and hence the pH of the blood consequently rise. Conversely an increase in partial pressure of carbon dioxide in the alveolar air will result in a fall in the pH of blood plasma. In practice the partial pressure of carbon dioxide in the alveolar air is controlled by the rate of pulmonary ventilation in relation to the rate of production of carbon dioxide by metabolic oxidation within the body. Increased ventilation (i.e. hyperventilation) will lower the partial pressure of carbon dioxide and raise the blood pH, while decreased ventilation raises the partial pressure, making the blood more acid (metabolic acidosis). Normally the respiratory centre controls the rate of ventilation to keep the partial pressure of carbon dioxide close to the normal value of 40 mmHg. 

Figure 3.4. The changes in blood chemistry occurring in metabolic acidosis. Arrow NA indicates the blood buffering of the acid load, arrow AB indicates the respiratory compensation for the acidaemia and arrow BC indicates the renal contribution to compensation, with retention of bicarbonate.

In such a case, the first stage is uncompensated metabolic acidosis, in which excess H is largely taken up by the blood buffers. The chemical reactions are shown in Table 3.5. Both types of buffer base, bicarbonate and non-bicarbonate, combine with hydrogen ions. For the bicarbonate system, the CO2 yielded (reaction 2) is lost via the lungs. As a result of reaction 2 in Table 3.5, bicarbonate is removed from the blood to be excreted as COj and the blood bicarbonate concentration falls. 

Role of bone buffering of acid, long time course because mineral in bone is inaccessible to the blood. Osteoporosis in chronic metabolic acidosis. 

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