What does the presence of lactic acid in a sample indicate about what process is occurring?

Salicylic acid products (e.g., Bazuka Extra Strength (26%), Occlusal (26%), Verrugon (50%)) and Salicylic acid/lactic acid combinations (Bazuka, Cuplex, Duofilm, Salactol, Salactac)

Before using a salicylic acid-based product,the affected area should be soaked in warm water and towelled dry. The surface of the wart or verruca should be rubbed with a pumice stone or emery board to remove any hard skin. A few drops of the product should be applied to the lesion, taking care to localise the application to the affected area. The procedure should be repeated daily. Salicylic acid can be recommended to most patients, although diabetics are a notable exception. Salicylic acid does not interact with any medicines. It can cause local skin irritation and, because, of its destructive action should be kept away from unaffected skin.

Lactic Acid

Lactate synthesis is a “necessary evil.” In glycolysis, conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase (G3PD) requires reduction of NAD to NADH. The NAD pool is small, and without rapid oxidation of NADH back to NAD, glycolysis would quickly stop at the G3PD step. Extramitochondrial oxidation of NADH back to NAD is accomplished by conversion of pyruvate to lactate via lactate dehydrogenase (LDH). Since the maximal reported rates of appearance of lactate in blood are only one tenth the FG fiber production rate, it is clear that maximal production rate far exceeds the efflux capacity and that high-intensity exercise must necessarily produce high intramuscular lactate concentration. Intramuscular [lactate] as high as 45–50 mMol/kg of cell water have been reported in man. Intracellular pH in muscle fibers is about 7.0, and decreases 0.4 to 0.8 pH units during intense exercise.

Lactate efflux from muscle occurs mainly by carrier-mediated lactate-proton cotransport and by simple diffusion of undissociated lactic acid. The former probably accounts for 50–90% of the lactate efflux, depending on fiber type and pH. There are three or more muscle lactate transporters. However, Km for lactate has not been found to differ significantly between fiber types, being around 30 mM. The high Km implies that a lot (perhaps most) of the lactate produced will be retained during exercise, regardless of fiber type. Retained lactate maintains an NAD/NADH ratio which stimulates oxidation, and ensures subsequent oxidation or gluconeogenesis in the muscle.

The fate of the lactate produced is primarily oxidative (55–70%), with as much as 90% of the labeled carbon in tracer lactate showing up as CO2 during active recovery from exercise. Lactate released from muscle enters exclusively oxidative tissues in which [lactate] is low (e.g., heart, diaphragm), is converted back to pyruvate and oxidized. Retained lactate is oxidized to generate the ATP needed to replenish phosphocreatine stores following exercise, and to restore normal distribution of Ca2+, Na+, and K+. In liver and kidney, about 5–15% is used for gluconeogenesis and subsequent glycogenesis. The balance is converted to alanine, glutamate, or other substances.

Lactic Acid and Other Markers

Although nonspecific, elevations in CSF lactic acid concentrations (>2.8 mmol/L) are potentially indicative of bacterial meningitis, and lactate may rise prior to the decline in glucose. Normal lactate levels (<2.8 mmol/L) are usually seen in patients with viral meningitides. A recent systematic review suggests that an elevated CSF lactate outperforms glucose, protein, and leukocyte count for diagnosing bacterial meningitis, but the strength of evidence is weak.12 At this time, we do not recommend using the CSF lactate as a definitive test, but it may have a role in the future.

C-reactive protein, CSF chloride, and the limulus lysate test do not have a defined utility in the evaluation of CNS infections.

Lactate Metabolism – An Integral Part of Normal Brain Function

Brain lactate is present at near 1 μmol g−1 concentration under normoxic conditions in vivo, and is continuously synthesized and broken down. Glucose and glycogen are the major metabolic precursors for lactate, which can be exported and serve as fuel for other cells. A small lactate efflux from the brain is observed normally. Rapid but small increases in brain lactate are observed in focal activation, consistent with a transient uncoupling of oxygen and glucose metabolism. Similar to that for glucose, lactate diffusion behavior is restricted, indicating that most tissue lactate is intracellular. Lactate is almost evenly distributed in the brain’s aqueous phase, owing to the large transport capacity of the abundant monocarboxylate transporters at the neuronal and glial cell membranes.

Lactic acid

Lactic acid, first used in 1943 for the treatment of dry skin,25 is a popular AHA found in several at-home products as well as prescription moisturizers for the treatment of severe ichthyosis or psoriasis. It is a unique hydroxy acid because it is a component of the natural moisturizing factor (NMF), which plays an important role in skin hydration. Studies of the activity of buffered 12% ammonium lactate lotion have documented the moisturizing ability of lactic acid.26 In addition, lactic acid imparts antiaging benefits, as implied by a double-blind vehicle-controlled study finding that an 8%l-lactic acid formula performed better than vehicle in treating photoaged skin, with statistically significant improvements in skin roughness, mottled hyperpigmentation, and sallowness.27 Lactic acid may have a sour milk smell that patients do not like; therefore, it is not very popular in facial products.

Lactate Clearance

Lactate clearance during rest and exercise occurs primarily by three processes: oxidation (50% to 80%), gluconeogenesis/glyconeogenesis (10% to 25%), and transamination (5% to 10%). All three processes involve the movement of lactate.18

As stated previously, at physiological pH more than 99% of the lactic acid produced quickly dissociates into lactate (La−) anions and protons (H+). Lactate moves readily between cytoplasm and mitochondria, muscle and blood, blood and muscle, active and inactive muscle, glycolytic and oxidative muscle, blood and heart, blood and liver, and blood and skin.20 Lactate moves between lactate-producing and lactate-consuming sites by means of intracellular and extracellular lactate shuttles.18 Transport across cellular and mitochondrial membranes occurs by facilitated exchange down concentration and hydrogen ion (pH) gradients using lactate transport proteins known as monocarboxylate transporters (MCTs).20

As of 1999, nine monocarboxylate transporters had been reported in the literature. MCT1 is abundant in oxidative skeletal and cardiac muscle fibers and mitochondrial membranes. MCT4 is most prevalent in the cell membranes of glycolytic skeletal fibers.

The intracellular lactate shuttle (Figure 3-4, A) involves the movement of lactate by MCT1 transporters between the cytoplasm, where it is produced, and the mitochondria. Once inside the mitochondria, lactate is oxidized to pyruvate and NAD+ is reduced to NADH + H+. The pyruvate and NADH + H+ proceed through aerobic metabolism/oxidation. This is a relatively new, and somewhat controversial, concept20–23 indicating that muscle cells can both produce and consume lactate at the same time.

Extracellular lactate shuttles act to move lactate among tissues (Figure 3-4, B). Muscle cell membrane lactate proteins (MCT1 and MCT4) move the lactate out of and into tissues. Intermuscularly, most lactate moves out of active fast-twitch glycolytic skeletal muscle cells (FOG and FG) and into active SO skeletal muscle cells. This can occur either by a direct shuttle between the skeletal muscle cells or through the circulation. Once lactate is in the bloodstream, it can also circulate to cardiac cells. During heavy exercise, lactate becomes the preferred fuel of the heart. In this manner glycogenolysis in one cell can supply fuel for another cell. In each case the ultimate fate of the lactate is oxidation to ATP, CO2, and H2O by aerobic metabolism.13,20,24

Lactate circulating in the bloodstream can also be transported to the liver, where it is reconverted by the processes of gluconeogenesis/glyconeogenesis into glucose or glycogen, respectively. Indeed, the liver appears to preferentially make glycogen from lactate as opposed to glucose. In human glycolytic muscle fibers (both FOG and FG) some of the lactate produced during high-intensity exercise is retained, and in the postexercise recovery period it is reconverted to glycogen in that muscle cell.4,25,26

Both oxidative and glycolytic fibers can also clear lactate by transamination. Transamination forms keto acids (including some Krebs cycle intermediates) and amino acids. The predominant amino acid produced is alanine. In turn, alanine can undergo gluconeogenesis in the liver.13,14

A small amount of lactate in the circulation moves from the blood to the skin and exits the body in sweat. Finally, some lactate remains as lactate circulating in the blood. This comprises the resting lactate level.

Oxidation is by far the predominant process of lactate clearance both during and after exercise. As stated previously, the accumulation of lactate in the blood depends on the relative rate of appearance (production) and disappearance (clearance), which in turn is directly related to the intensity and duration of the exercise being done.

Lactate

Lactate is not a traditional blood gas value. However lactate is routinely measured by many blood gas analyzers, so a brief basic discussion of its value is warranted. Analyzers equipped to measure lactate will directly measure the blood with a biosensor utilizing amperometric principles.106 Lactate is the result of the metabolism of glucose during tissue hypoxia whereby lactate, ATP, and water are produced.127 Tissue hypoxia and poor tissue perfusion can lead to hyperlactatemia, which can also result from other mechanisms.128 Blood lactate levels are a reflection of the difference between production and elimination, with the liver being responsible for the majority of lactate clearance.128 Normal blood lactate levels for the term infant depend on local established values and have been reported at <2.0 mmol/L.129 Arterial, venous, and capillary values for lactate levels have been used clinically, with most reporting good correlation between the sample types.127,130 Samples should be run within 15 minutes to prevent lactate levels from increasing prior to testing.127 Lactate values have a useful role in the assessment of the newborn. Lactate measured in umbilical cord blood was shown to agree with pH and BE and has similar predictive value for short-term morbidities compared to pH and BE.131 A retrospective study of term infants with intrapartum asphyxia comparing the predictive value of pH, base deficit, and lactate for the incidence of moderate to severe hypoxic encephalopathy (HIE) showed that the highest lactate levels in the first hours of life are important predictors of moderate to severe HIE.127 Measurement of serum lactate is very helpful in differentiating increased acid production (e.g., due to inadequate tissue oxygen delivery) from loss of bicarbonate, such as occurs in renal tubular acidosis.

Lactate

Lactate is an important energy source in the fetal heart, brain, and skeletal muscle. Fetal levels of lactate are higher than maternal levels. The placenta may be a source of lactate even when oxygen supplies are adequate. However, the placenta is also an important site for clearance of fetal lactate, especially in cases of fetal hypoxia. Lactate is transported across cell membranes by members of the monocarboxylate transporter (MCT) family (SLC16), which mediate H+–lactate co-transport. Both the MVM170 and BM170 efficiently transport lactate in the presence of a proton gradient. The predominant MCT isoform in the MVM is MCT4, whereas MCT1 is the main form in the BM.170

It is believed that the primary route for placental elimination of metabolically produced protons by the fetus involves H+–lactate co-transport across the BM, followed by extrusion of protons in NHE-based exchange for sodium across the MVM (Figure 39.11). It is also possible that excitatory amino acid transporters, which are active in the BM,171 contribute to the transport of protons from the fetal compartment into the syncytiotrophoblast across the BM. These transporters mediate the cellular uptake of anionic amino acids, coupled to the co-transport of Na+ and H+.

Lactate Utilization (Removal): Gluconeogenesis and Oxidation

Clearance of lactate after maximal exercise depends on recovery intensity, with faster clearance occurring with active than with passive recovery.15 In critically ill patients, lactate clearance (i.e., volume of plasma that is cleared off of lactate per unit of time) has been estimated by quantifying the disposal of infused sodium L-lactate and was found to be approximately 800 to 1800 mL/minute. Although many organs consume lactate, the liver and the kidney represent the major sites of lactate uptake and clearance as they metabolize approximately 53%15 and 30%16–18 of daily lactate production, respectively. Lactate is metabolized by two main mechanisms: First, lactate can be used as a substrate to regenerate glucose by gluconeogenesis, a process that is exclusive to liver and the kidney. Second, at least 50% of circulating lactate is removed and metabolized by means of oxidation during resting conditions.19 Unlike gluconeogenesis, which is restricted to liver and kidney, oxidation can take place in many organs, including the heart, brain, and skeletal muscle.

Lactic Acid

Lactic acid is the predominant acid in the vagina and responsible for the vaginal pH in most healthy women to be <4.5. The majority of the lactic acid comes from the anaerobic glycolysis of glycogen degradation products by Lactobacilli, as well as by other lactic acid–producing bacteria. The vaginal epithelial cells also release a relatively minor amount of lactic acid into the vaginal lumen. L. crispatus, L. gasseri, and L. jensenii each produce both the D and L isomeric form of lactic acid. In contrast, L. iners, other bacteria, and epithelial cells only produce the L isomer [4,25,26].

Unlike similar acidic compounds, lactic acid possesses unique immunological properties that downregulate proinflammatory immune responses. This has been most elucidated in the cancer literature, where production of lactic acid by tumors has been shown to decrease T lymphocyte activity, inhibit the production of proinflammatory cytokines, and induce macrophages to revert to an antiinflammatory phenotype (summarized in Ref. [27]). It has also been demonstrated that lactic acid production by bacteria present in the gastrointestinal tract reduces local proinflammatory immunity [28].

It is, therefore, reasonable to project that lactic acid in the vagina similarly functions to diminish the magnitude and facilitate the resolution of inflammatory responses at this site that may be induced due to daily exposure to microorganisms and chemicals in the external environment. Especially during pregnancy, inflammation may interfere with the programmed series of events needed for fetal maturation, as well as induce a premature termination of gestation [5,29]. Thus, the ability of lactic acid to inhibit or kill potential microbial pathogens, while concomitantly blocking inflammation, highlights its utility as a key factor to promote successful pregnancy outcomes.

Addition of D lactic acid by vaginal Lactobacilli further contributes to well-being. This isomer regulates the rate of lactic acid flow into and out of cells by modulating the activity of extracellular matrix metalloproteinase inducer (EMMPRIN), an essential cofactor for monocarboxylate transporter activity [26]. As its name implies, EMMPRIN also induces production of metalloproteinase enzymes that degrade the cellular matrix and facilitate bacterial migration from the lower to the upper genital tract [26]. Thus, the regulation of EMMPRIN production by d-lactic acid facilitates epithelial cell survival in an acidic environment by preventing an intracellular acid buildup and by downregulating deleterious matrix metalloproteinase production.