Acidosis/increased acidity

Lactic acid also cuts (truncates) the last 3 amino acids off the 70 amino acid chain of "some" of the surviving IGF-1 and creates Des (1-3) IGF-1. So acidosis increases GH/IGF-1 production in the liver, "unbinds" IGF-1 locally in the muscle being trained (burned), destroys some of the IGF-1, and converts some IGF-1 into Des (1-3) IGF-1. 

Nonmetal oxides dissolve in water to give acid solutions. The most physiologically important example is carbon dioxide. Of course, you already know this. Buildup of carbon dioxide in the blood results in acidosis. This is not necessarily a bad thing. In cellular tissue, where the carbon dioxide concentration is relatively high, the increased acidity slightly alters the structure of hemoglobin, and facilitates the release of oxygen. 

Laboratory tests on a sick child reveal a low white blood cell count, metabolic acidosis, increased anion gap, and mild hyperammonemia. Measurement of plasma amino acids reveals elevated levels of glycine, and measurement of urinary organic acids reveals increased amounts of propionic acid and methyl citrate. Which of the following processes is most likely ... 

Metabolic acidosis with an increased SAG commonly results from increased endogenous organic acid production. In lactic acidosis, lactic acid accumulates as a by-product of anaerobic metabolism. Accumulation of the ketoacids /S-hydroxybutyric acid and acetoacetic acid defines the ketoacidosis of uncontrolled diabetes mellitus, alcohol intoxication, and starvation (see Table 51-5). In advanced renal failure, ac-cumulation of phosphate, sulfate, and organic anions is responsible for the increased SAG, which is usually less than 24 mEq/L." The severe metabolic acidosis seen in myoglobinuric acute renal failure caused by rhabdomyolysis may be caused by the metabolism of large amounts of sulfur-containing amino acids released from myoglobin. 

Buffers in dairy rations are compounds that neutralize excess acid within the animal s digestive system. The increased emphasis on production and efficiency in dairy cows has lead to an increased use of high concentrate or high-energy rations. Since these rations have more easily fermentable starch in them, this results in increased acid production in the rumen and subsequent acidosis. Higher acidity can result in reduced feed intake, lower milk production, and decreased butterfat. It can also endanger the animal s health and cause liver abscesses, fatty liver syndrome, rumenitis, and laminitis. 

Systemic acidosis increases the potency of phenobarbital by shifting the ionization equilibrium to the left. Because the drug is a weak acid, a lowering of physiologic pH results in an increase in the amount of nonionized drug and an increase in the amount of drug which enters the CNS. (Recall that a drug may only cross the blood-brain barrier in nonionized form.)... 

In these hypercatabolic states, skeletal muscle protein synthesis decreases, and protein degradation increases. Oxidation of BCAA is increased and glutamine production enhanced. Amino acid uptake is diminished. Cortisol is the major hormonal mediator of these responses, although certain cytokines may also have direct effects on skeletal muscle metabohsm. As occurs during fasting and metabolic acidosis, increased levels of cortisol stimulate ubiquitin-mediated proteolysis, induce the synthesis of glutamine synthetase, and enhance release of amino acids and glutamine from the muscle cells. 

As stated earlier, the acidity or alkalinity of a substance is referred to as the pH. 2 The normal pH of blood is between 7.35 and 7.45. High fever, taking too many antacids, or vomiting can cause the pH of blood to increase to above 7.46, a condition called alkalosis. If, on the other hand, the blood pH drops to below 7.34, then acidosis occurs. Acid-base balance is one of the most important aspects of homeostasis. The acid-base balance is concerned primarily with regulating the hydrogen ion concentration. The normal blood plasma pH range of 7.35-7.45 is maintained in the body when a 1 20 ratio of H COj to HCOj is maintained. 

When excessive acids (i.e., hydrogen ions) are present in body fluids relative to the bases (i.e., hydroxide ions) or reduced bases/alkali occur relative to the hydrogen ions, the patient is in a state of acidosis. The most common acid in the body is carbonic acid (H COj). When the patient is in a state of acidosis, the body seeks to buffer or normalize the state by supplying bicarbonate to balance the hydrogen ions. Since the normal ratio of bicarbonate to carbonic acid (i.e., hydrogen ions) is 20 1, any increased acid content changes the ratio, resulting in an acidotic state. 

In acute severe systemic intoxication abnormalities of routine clinical chemistry are usually present such as metabolic acidosis, increased anion gap, cytopenia, hypoglycemia, hyperammonemia (which can mask acidosis), lactic acidemia, elevations of triglycerides and free fatty acids, and ketosis. Testing for ketonuria is an especially simple and useful first line investigation. In most newborns as well as in older children with organic acid disorders, including some patients with fatty acid oxidation defects, there is pronounced ketonuria. Ketonuria is only rarely observed even in very sick newborns without metabolic disease. 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

Metabolic acidosis is caused by the release into the bloodstream of excessive amounts of lactic acid and other acidic byproducts of metabolism. These acids enter the bloodstream, react with hydrogen carbonate ion to produce H2CX)5, and shift the ratio HC03 /H2C03 to a lower value. Heavy exercise, diabetes, and fasting can all produce metabolic acidosis. The normal response of the body is to increase the rate of breathing to eliminate some of the CO,. Thus, we pant heavily when running uphill. 

Excretion into urine of ammonia produced by renal mbu-lar cells facilitates cation conservation and regulation of acid-base balance. Ammonia production from intracellular renal amino acids, especially glutamine, increases in metabolic acidosis and decreases in metabolic alkalosis. 

When blood pH falls below normal limits, the condition is termed acidosis. A number of body malfunctions can lead to acidosis, including diabetes, kidney failure, and persistent diarrhea. Temporary acidosis can result from prolonged vigorous exercise. These situations stimulate production of CO2, increasing the acidity of the blood. 

This isotonic volume expander contains sodium, potassium, chloride, and lactate that approximates the fluid and electrolyte composition of the blood. Ringer s lactate (also known as lactated Ringer s or LR) provides ECF replacement and is most often used in the perioperative setting, and for patients with lower GI fluid losses, burns, or dehydration. The lactate component of LR works as a buffer to increase the pH. Large volumes of LR may cause metabolic alkalosis. Because patients with significant liver disease are unable to metabolize lactate sufficiently, Ringer s lactate administration in this population may lead to accumulation of lactate with iatrogenic lactic acidosis. The lactate is not metabolized to bicarbonate in the presence of liver disease and lactic acid can result. 

Metabolic acidosis is characterized by a decrease in serum HC03. The anion gap is used to narrow the differential diagnosis, as this acidosis may be caused by addition of acids (increased anion gap) or loss of HC03 (normal anion gap). The compensation for metabolic acidosis is an increase in ventilation with a decrease in arterial C02. 

It is important to realize that the serum HCO, concentration may be affected by the presence of unmeasured endogenous acids (lactic acidosis or ketoacidosis). Bicarbonate will attempt to buffer these acids, resulting in a 1 mEq loss of serum HCO, for each 1 mEq of acid titrated. Because the cation side of the equation is not affected by this transaction, the loss of serum HC03 results in an increase in the calculated anion gap. Identification of an increased anion gap is very important for identifying the etiology of the acid-base disorder. The concept of the increased anion gap will be applied later in the case studies section. 

The normal UAG ranges from 0 to 5 mEq/L (mmol/L) and represents the presence of unmeasured urinary anions. In metabolic acidosis, the excretion of NH4+ and concurrent CP should increase markedly if renal acidification is intact. This results in UAG values from -20 to -50 mEq/L (mmol/L). This occurs because the urinary CP concentration now markedly exceeds the urinary Na+ and K+ concentrations. Diagnoses consistent with an excessively negative UAG include proximal (type 2) renal tubular acidosis, diarrhea, or administration of acetazo-lamide or hydrochloric acid (HC1). Excessively positive values of the UAG suggest a distal (type 1) renal tubular acidosis. 

Biguanides such as metformin are thought to inhibit mitochondrial oxidation of lactic acid, thereby increasing the chance of lactic acidosis occurring. Fortunately, the incidence of lactic acidosis in clinical practice is rare. Patients at greatest risk for developing lactic acidosis include those with liver disease or heavy alcohol use, severe infection, heart failure, and shock. Thus, it is common practice to evaluate liver function prior to initiation of metformin. 

Factors that can predispose patients to developing metabolic bone disease include deficiencies of phosphorus, calcium, and vitamin D vitamin D and/or aluminum toxicity amino acids and hypertonic dextrose infusions chronic metabolic acidosis corticosteroid therapy and lack of mobility.35,39 Calcium deficiency (due to decreased intake or increased urinary excretion) is one of the major causes of metabolic bone disease in patients receiving PN. Provide adequate calcium and phosphate with PN to improve bone mineralization and help to prevent metabolic bone disease. Administration of amino acids and chronic metabolic acidosis also appear to play an important role. Provide adequate amounts of acetate in PN admixtures to maintain acid-base balance. 

Chemoreceptor response to increased arterial hydrogen ion concentration. An increase in arterial hydrogen ion concentration, or a decrease in arterial pH, stimulates the peripheral chemoreceptors and enhances ventilation. This response is important in maintaining acid-base balance. For example, under conditions of metabolic acidosis, caused by the accumulation of acids in the blood, the enhanced ventilation eliminates carbon dioxide and thus reduces the concentration of H+ ions in the blood. Metabolic acidosis may occur in patients with uncontrolled diabetes mellitus or when tissues become hypoxic and produce lactic acid. An increase in arterial hydrogen ion concentration has no effect on the central chemoreceptors. Hydrogen ions are unable to cross the blood-brain barrier. 

Beyond this point, during more severe exercise associated with anaerobic metabolism, minute ventilation increases faster than the rate of oxygen consumption, but proportionally to the increase in carbon dioxide production. The mechanism of the ventilatory response to severe exercise involves metabolic acidosis caused by anaerobic metabolism. The lactic acid produced under these conditions liberates an H+ ion that effectively stimulates the peripheral chemoreceptors to increase ventilation. 

Salicylate or aspirin overdose is characterized by tinnitus, confusion, rapid pulse rate, and increased respiration. The decreased partial pressure of arterial C02 (Pco2) plus increased fixed acids first cause alkalosis, which is followed by metabolic acidosis, dehydration, and loss of fixed bases. The picture may resemble diabetic acidosis, but the history of salicylate ingestion and blood salicylate levels above. 540 mg/100 mL clinch the diagnosis. 

---