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Transcript
LACTIC ACIDOSIS Cadel Evans, 2011 winner of the Tour de France, the oldest, most prestigious and greatest endurance event in world sport - amoung the many great Australian sporting achievements- this was one of the greatest! Here Cadel stands on the winner’s podium in Paris, with Ms Tina Arena belting out a powerful and emotional rendition of the national anthem. “For Cadel to come to Europe and spend so much time chasing his dream shows what he is made of” Tina Arena to the French Media, (in French) “I think that’s the ultimate dream of a Tour rider, to stand on the Champs-Elysees with an Australian singing the national anthem ... it’s not a dream that comes true for many Australians…This win is for everyone in our country!” Cadel Evans During strenuous exercise oxygen stores are rapidly depleted and anaerobic metabolism must be relied on for the provision of energy. This occurs however with the development of an “oxygen debt” mainly in the form of accumulated lactic acid. It is this lactic acid, which in a large degree accounts for the feeling of fatigue in exercise. Trained athletes such as Australia’s Tour de France winner Cadel Evans are able to increase the oxygen consumption of their muscles to a greater degree than untrained individuals and hence are capable of greater exertion without depleting glycogen stores and accumulating lactic acid to the extent that occurs in an untrained individual. Athletes can also help minimize their lactic acid production during exercise by increasing their glycogen stores before an event by consuming specially planned diets of large amounts of carbohydrate and refraining from exercise 48 hours prior to the event…after the event carbohydrate loading takes a somewhat different form …Champagne on the Champs-Elysees! LACTIC ACIDOSIS Introduction Lactic acidosis is conventionally defined as the combination of an increased blood lactate concentration and acidemia. It is one of the causes of an increased anion gap metabolic acidosis. Overall critically ill patients with lactic acidosis tend to have high mortality if their lactate levels are significantly elevated (>8 mmols/L). In each individual case however, the actual prognosis will be completely dependent on the underlying condition, with the initial degree of lactic acidosis being a clinically useful indicator of the severity of the shock/hypoxia. Physiology Under normal aerobic conditions glucose is converted to pyruvate, which is in turn converted to acetyl-CoA. Acetyl-CoA then combines with oxaloacetate to form citrate, and so enters the Krebs cycle. The Krebs cycle of biochemical reactions then produces water, CO2 and most importantly, ATP, the primary cellular energy source. Under anaerobic conditions, or when the metabolic demands of the cells exceed the oxygen delivery capacity of the body, pyruvate is unable to enter the Krebs cycle to produce ATP for cellular energy. Instead it is converted to lactic acid, by which some ATP is produced in compensation, although this is of much lesser degree than that which is obtained from aerobic metabolism, and is at the expense of an increasing lactic acidosis. Pathology Lactic acidosis occurs when the production of lactate exceeds the systemic metabolism of it. Lactate is metabolized by the liver, kidneys, skeletal muscle, brain, and the red blood cells. When the acidosis becomes severe cellular dysfunction will occur. Classification The Cohen and Woods 2 classification is the most commonly used. Type A The most common form is due to anaerobic metabolism secondary to inadequate tissue oxygenation due to the following two causes: 1. Shock from any cause: ● 2. With inadequate tissue perfusion and / or abnormal oxygen utilization. Tissue hypoxia from any cause: ● Hypoxic hypoxia. ● Anaemic hypoxia. ● Stagnant hypoxia. ● Histotoxic hypoxia. ● Low inspired oxygen concentration Type B Here tissue oxygenation and perfusion is adequate but lactic acidosis is still present. There are 3 subtypes: B1: Associated with “systemic” disorders that result in increased levels of lactate by mechanisms other than tissue hypoxia or shock. 1. Liver failure. ● 2. A failure to metabolize lactate. Renal failure ● A failure to metabolize lactate and excrete 3. Some malignant conditions (leukemia, lymphomas) 4. Thiamine deficiency. ● A failure of the pyruvate to oxaloacetate pathway, (hence more pyruvate is converted to lactate). 5. Diabetes. 6. Sepsis. B2: Drugs and toxins. 1. Biguanides. 2. Ethanol. 3. Methanol. B3: Rare inborn enzyme errors of metabolism defects. Investigations In cases of lactic acidosis: 1. There will be: ● Metabolic acidosis with increased anion gap. ● Elevated serum lactate. ♥ ● 2. Normal value range of lactate is 0.63-2.44 mmol / L. Absent (or minimal ketones, in pure cases of lactic acidosis). Lactic acidosis is caused by accumulation of lactate and H+ ions. ● It is not lactate that causes acidosis, but the attendant H+ ions, (lactate levels may be increased without an acidosis, eg. infusion of Hartman’s solution). ● Therefore, increased lactate is merely an indication that the observed acidosis could be due to lactic acid production. Interpretation: Overall critically ill patients with lactic acidosis tend to have high mortality if their lactate levels are significantly elevated (>8 mmols/L). In each individual case however, the actual prognosis will be completely dependent on the underlying condition, with the initial degree of lactic acidosis being a clinically useful indicator of the severity of the shock/hypoxia. Serial assessments will then allow for one way of evaluating the response to therapy. It is also important to assess lactic acidosis in clinical context. Healthy athletes for example can develop significant lactic acidosis during strenuous exercise, as a normal self-limited observation. Management 1. 2. Treat the underlying cause: ● The treatment of patients who have lactic acidosis, involves the treatment of the underlying cause, not the lactic acidosis itself. ● In type A lactic acidosis, this will mean aggressive resuscitation measures, to improve tissue oxygenation and /or perfusion. ● Drugs or toxins known to cause lactic acidosis (such as metformin) must be ceased immediately, if lactic acidosis is detected. Bicarbonate: ● The use of bicarbonate in lactic acidosis remains uncertain and controversial ● In practice it is often given when the acidosis is very severe or the patient is very unstable, however its benefit has never been convincingly demonstrated. The priority will always remain aggressive treatment of the underlying cause. Victory! References 1. Cooper D. J, Nichol A.D. Lactic Acidosis, in OH. T.E, “Intensive Care Manual”, 6th ed Butterworth Heinemann, 2009. 2. Cohen R.D, Woods HF. Lactic acidosis revisited. Diabetes 1983; 32 181-191. 3. Ganong, Review of Medical Physiology 17th Ed, p. 65 Dr J. Hayes Reviewed August 2011.