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lactic acidosis

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  1. 1. Lactic Acidosis Dr. tongjun Ma Emergency department of Tianjin Medical University General Hospital
  2. 2. Introduction <ul><li>LA are important in emergency medicine. </li></ul><ul><ul><li>common complication of many severe illness including sepsis , cardiac failure, respiratory failure, hepatic failure, cancer, AIDS, seizure, poisoning and drug therapy </li></ul></ul><ul><ul><li>change into multiple organ dysfunction syndrome and the mortality rate is more than 75% </li></ul></ul>
  3. 3. Content <ul><li>Definition </li></ul><ul><li>Pathophysiology </li></ul><ul><li>Etiology and categories </li></ul><ul><li>Manifestation </li></ul><ul><li>Diagnosis </li></ul><ul><li>Treatment </li></ul><ul><li>Prognosis </li></ul><ul><li>8. D- Lactic Acidosis </li></ul>
  4. 4. 1. Definition <ul><li>LA is a metabolic acidosis caused by lactic acid accumulation, pH ↓ + Lactate↑ </li></ul><ul><li>plasma lactate concentration </li></ul><ul><ul><li>Normal: 0.5~1.5 mmol/L, average: 1 mmol/L </li></ul></ul><ul><ul><li>Hyperlactatemia: 2~5 mmol/L </li></ul></ul><ul><ul><li>Lactic acidosis: >5 mmol/L </li></ul></ul>
  5. 5. 2. Pathophysiology (1) Lactic acid production <ul><li>Lactate is a key substrate which is simultaneously produced and used by the body tissues </li></ul><ul><ul><li>All tissues can produce lactic acid, brain, erythrocytes and skeletal muscle are the main organs </li></ul></ul><ul><ul><li>Basal lactate production is high, about 1 mmol/kg per hour(15~20 mmol/kg•d, or 1400 mmol per day for a 70 kg person) </li></ul></ul><ul><ul><li>Under some conditions, the production rate can increase 50 times. In severe exercise, lactate levels can rise to very high levels eg up to 30 mmol/L. </li></ul></ul>
  6. 6. <ul><li>Main pathways of lactate metabolism. </li></ul><ul><li>lactic acid is a metabolic dead-end </li></ul><ul><ul><li>Pyruvate is the sole immediate precursor </li></ul></ul><ul><ul><li>Pyruvate is the only route of metabolic transformation </li></ul></ul>
  7. 7. <ul><li>There is a balance between pyruvate and lactic acid </li></ul><ul><ul><li>catalyzed by LDH (lactate dehydrogenase) </li></ul></ul><ul><ul><li>When concentration of pyruvate or NADH increase , the concentration of lactic acid will increase </li></ul></ul><ul><ul><li>Under normal conditions, the lactate/pyruvate ratio ranges from 4:1 to 10:1 </li></ul></ul>
  8. 8. <ul><li>From glucose and alanine </li></ul><ul><ul><li>The largest part originates from glucose (or glycogen) via the reactions of glycolysis </li></ul></ul><ul><ul><li>A smaller part originates from transamination of alanine </li></ul></ul>
  9. 9. <ul><li>Pyruvate can have several metabolic fates </li></ul><ul><ul><li>oxidation in the tricarboxylic acid cycle for energy production </li></ul></ul><ul><ul><li>transformation into glucose via the gluconeogenesis pathways </li></ul></ul>
  10. 10. <ul><li>Under aerobic conditions, pyruvate change into acetyl CoA. Acetyl CoA change into CO 2 and NADH through the tricarboxylic acid cycle in the matrix of the mitochondria. </li></ul><ul><li>Under anaerobic conditions, pyruvate change into lactic acid in the cellular cytosol. </li></ul>
  11. 11. 2. Pathophysiology (1) Lactic acid production <ul><li>Pathological lactate production occurs when </li></ul><ul><ul><li>inadequate tissue oxygen supply </li></ul></ul><ul><ul><li>defective pyruvate clearance </li></ul></ul><ul><ul><li>increased pyruvate or NADH production </li></ul></ul>
  12. 12. 2. Pathophysiology (2) Lactic acid destruction <ul><li>The half-life of serum lactate is about 60 minutes </li></ul><ul><li>Cleared in three ways </li></ul><ul><ul><li>Gluconeogenesis </li></ul></ul><ul><ul><li>Oxidation </li></ul></ul><ul><ul><li>Excretion </li></ul></ul><ul><ul><ul><li>renal threshold is 6~10 mmol/L </li></ul></ul></ul>
  13. 13. 2. Pathophysiology (2) Lactic acid destruction <ul><li>Lactate is utilized mainly by the liver and kidney. </li></ul><ul><ul><li>About 65% of lactate was cleared by liver. </li></ul></ul><ul><ul><li>The kidneys can remove 10~20% of the total lactate. </li></ul></ul>
  14. 14. 2. Pathophysiology (3) Mechanisms <ul><li>Lactic acidosis can occur due to </li></ul><ul><ul><li>excessive tissue lactate production </li></ul></ul><ul><ul><li>impaired hepatic metabolism </li></ul></ul><ul><ul><li>In most clinical cases both processes are contributing to the development of the acidosis. </li></ul></ul>
  15. 15. 3. Etiology and Categories <ul><li>Two types </li></ul><ul><ul><li>Type A </li></ul></ul><ul><ul><ul><li>obvious tissue hypoxia </li></ul></ul></ul><ul><ul><ul><li>Common </li></ul></ul></ul><ul><ul><li>Type B </li></ul></ul><ul><ul><ul><li>tissue hypoxia is not apparent </li></ul></ul></ul><ul><ul><ul><li>Rare </li></ul></ul></ul><ul><ul><ul><li>Three subtypes: B1, B2, B3 </li></ul></ul></ul><ul><li>developed by Cohen and Woods in 1976 and it is widely accepted now </li></ul>
  16. 16. 3. Etiology and Categories: type A <ul><li>Tissue hypoxaemia </li></ul><ul><ul><li>severe anemia </li></ul></ul><ul><ul><li>carbon monoxide poisoning </li></ul></ul><ul><li>Tissue hypoperfusion </li></ul><ul><ul><li>with clinical evidence </li></ul></ul><ul><ul><ul><li>Hypotension </li></ul></ul></ul><ul><ul><ul><li>cyanosis </li></ul></ul></ul><ul><ul><ul><li>cool and clammy extremities </li></ul></ul></ul>
  17. 17. 3.Etiology and Categories <ul><li>76 years old, female </li></ul><ul><li>chief complain: sudden severe pain across her mid-abdomen after dinner and moved to her left flank, vomiting </li></ul><ul><li>past history: hypertension, kidney stone </li></ul><ul><li>Laboratory data: WBC count 11000 , sodium 140 mEq/L, serum creatinine 1mg/dl, urine WBC +, urine ketones “trace” </li></ul><ul><li>Ultrasound: hydronephrosis </li></ul><ul><li>After admission, she developed shaking chills, T 39℃ , blood pressure became progressively lower and was hard to detect several hours later </li></ul><ul><li>serum lactate level was 7.4 , pH 7.24 </li></ul><ul><li>Diagnosis: Urinary tract infection, septic shock, LA </li></ul>
  18. 18. 3. Etiology and Categories (2) type B1 <ul><li>B1:with underlying disease </li></ul><ul><ul><li>liver diseases, renal failure ( glyconeogenesis) </li></ul></ul><ul><ul><li>malignancy (eg, leukemia, lymphoma, lung cancer) </li></ul></ul><ul><ul><ul><li>Malignant cells produce more lactate </li></ul></ul></ul><ul><ul><li>Seizures, severe asthma (enhanced metabolic rate , increased Oxygen Consumption ) </li></ul></ul>
  19. 19. 3. Etiology and Categories (2) type B1 <ul><li>B1:with underlying disease </li></ul><ul><ul><li>thiamine deficiency </li></ul></ul><ul><ul><ul><li>coenzyme of pyruvate dehydrogenase, can lead to defective pyruvate metabolism </li></ul></ul></ul><ul><ul><ul><li>Patients receiving total parenteral nutrition (TPN) without intravenous multivitamins (MVIs) supplementation are at risk for thiamine deficiency and life-threatening complications associated with severe deficiency of thiamine </li></ul></ul></ul>
  20. 20. 3. Etiology and Categories (2) type B1 <ul><li>B1:with underlying disease </li></ul><ul><ul><li>thiamine deficiency </li></ul></ul><ul><ul><ul><li>a 32-year-old man underwent a total coloproctectomy with ileostomy as treatment for fulminant ulcerative colitis. </li></ul></ul></ul><ul><ul><ul><li>TPN was initiated immediately postoperatively and included 2087 ml per day of amino acids (92 g) and dextrose (382.5 g) with 21 g fat emulsion, electrolytes, and minerals per day; however, no MVIs were added to the solution. </li></ul></ul></ul>
  21. 21. 3. Etiology and Categories (2) type B1 <ul><li>B1:with underlying disease </li></ul><ul><ul><li>thiamine deficiency </li></ul></ul><ul><ul><ul><li>Attempts to introduce clear liquids orally on 4th and fifth days after operation were unsuccessful because of persistent severe anorexia, nausea, and vomiting. </li></ul></ul></ul><ul><ul><ul><li>7 days after operation ,an upper gastrointestinal barium imaging study revealed delayed transit time, but no mechanical obstruction. </li></ul></ul></ul>
  22. 22. 3. Etiology and Categories (2) type B1 <ul><li>B1:with underlying disease </li></ul><ul><ul><li>thiamine deficiency </li></ul></ul><ul><ul><ul><li>19 days after operation, TPN was continued without MVIs. the patient was lethargic and weak, and abnormal laboratory findings included severe acidosis :pH 6.87 ; HCO3, 5 mEq/L ; pCO2, 28 mm Hg pO2, 131 mm Hg ; and serum lactic acid of 16 mmol/L serum ketones were negative. </li></ul></ul></ul><ul><ul><ul><li>Lactic acidosis of unknown etiology was diagnosed. </li></ul></ul></ul>
  23. 23. 3. Etiology and Categories (2) type B1 <ul><li>B1:with underlying disease </li></ul><ul><ul><li>thiamine deficiency </li></ul></ul><ul><ul><ul><li>During the next 8 hours, 600 mEq/L of bicarbonate was administered with only modest elevation of pH (to 7.20) . </li></ul></ul></ul><ul><ul><ul><li>Because the patient's clinical condition continued to deteriorate, an exploratory laparotomy was performed; however, no focus of infection or bowel necrosis was found. </li></ul></ul></ul>
  24. 24. 3. Etiology and Categories (2) type B1 <ul><li>B1:with underlying disease </li></ul><ul><ul><li>thiamine deficiency </li></ul></ul><ul><ul><ul><li>An analysis for serum thiamine measured the lowest detectable level of 0.2 mg/dL (normal: 1.1-1.6 mg/dL), and 400 mg of thiamine was administered intravenously. </li></ul></ul></ul><ul><ul><ul><li>Two hours later, a blood gas specimen contained a serum pH of 7.50 and an HCO3 of 11.3 mEq/L. Acid/base and clinical status improved; a second dose of 400 mg thiamine was administered intravenously, and pH, pCO2, and HCO3 levels returned to normal. </li></ul></ul></ul>
  25. 25. 3.Etiology and Categories (3)type B2 <ul><li>B2: drugs and toxins </li></ul><ul><ul><li>Biguanides </li></ul></ul><ul><ul><ul><li>phenformin, metformin </li></ul></ul></ul><ul><ul><ul><li>Antihyperglycemic agent, used to treat type 2 diabetes (overweight, obesity) </li></ul></ul></ul><ul><ul><ul><li>decrease gluconeogenesis </li></ul></ul></ul><ul><ul><ul><li>probably interferes with mitochondrial function </li></ul></ul></ul>
  26. 26. 3.Etiology and Categories (3)type B2 <ul><li>B2: drugs and toxins </li></ul><ul><ul><li>biguanides </li></ul></ul><ul><ul><ul><li>The estimated rate of phenformin-associated lactic acidosis ranged from 40 to 64 cases per 100,000 person-years, which has a 50% fatality rate. </li></ul></ul></ul><ul><ul><ul><li>In 1977, phenformin was banned by the FDA. </li></ul></ul></ul><ul><ul><ul><li>With the Cessation of phenformin therapy, lactic acidosis in diabetes become uncommon </li></ul></ul></ul>
  27. 27. 3.Etiology and Categories (3)type B2 <ul><li>B2: drugs and toxins </li></ul><ul><ul><li>biguanides </li></ul></ul><ul><ul><ul><li>The lactic acidosis rate in metformin users is much lower, 9 cases per 100,000 person-years. </li></ul></ul></ul><ul><ul><ul><li>Metformin is contraindicated because of an increased risk of lactic acidosis : </li></ul></ul></ul><ul><ul><ul><ul><li>elevated serum creatinine levels (> 1.5 mg/dl for males and > 1.4 mg/dl for females) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>hepatic impairment </li></ul></ul></ul></ul><ul><ul><ul><ul><li>hypoxic states (shock, severe heart failure) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>excessive alcohol intake </li></ul></ul></ul></ul>
  28. 28. 3.Etiology and Categories (3)type B2 <ul><li>B2: drugs and toxins </li></ul><ul><ul><li>biguanides </li></ul></ul><ul><ul><ul><li>Special X-ray tests that require the injection of contrast media often cause kidneys to be temporarily less efficient in clearing lactic acid </li></ul></ul></ul><ul><ul><ul><li>To lessen the risk for lactic acidosis, metformin is stopped before the examination and restarted about 48 hours afterwards if the renal function is normal. </li></ul></ul></ul>
  29. 29. 3.Etiology and Categories (3)type B2 <ul><li>B2: drugs and toxins </li></ul><ul><ul><li>anti-retrovirus drugs </li></ul></ul><ul><ul><ul><li>In 1996, AIDS patients were treat ed with anti-retrovirus drugs. </li></ul></ul></ul><ul><ul><ul><li>s hortly thereafter, reports of fatal lactic acidosis began to appear . </li></ul></ul></ul>
  30. 30. 3.Etiology and Categories (3)type B2 <ul><li>B2: drugs and toxins </li></ul><ul><ul><li>anti-retrovirus drugs </li></ul></ul><ul><ul><ul><li>20% ~ 80% of individuals develop some metabolic abnormalities </li></ul></ul></ul><ul><ul><ul><ul><li>Changes in body habitus ( Central obesity) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>increased plasma lipids </li></ul></ul></ul></ul><ul><ul><ul><ul><li>glu cose intolerance and insulin resistance </li></ul></ul></ul></ul><ul><ul><ul><ul><li>h yperlactatemia and lactic acidosis </li></ul></ul></ul></ul>
  31. 31. 3.Etiology and Categories (3)type B2 <ul><li>B2: drugs and toxins </li></ul><ul><ul><li>anti-retrovirus drugs </li></ul></ul><ul><ul><ul><li>m itochondrial toxicity </li></ul></ul></ul><ul><ul><ul><ul><li>m itochondria has his own DNA and h ave their own DNA replicating enzyme </li></ul></ul></ul></ul><ul><ul><ul><li>incidence rate : Stavudine( d4T ) > zidovudine( AZT ) / didanosine ( ddI ) > lamivudine ( 3TC ) </li></ul></ul></ul>
  32. 32. 3.Etiology and Categories (3)type B2 <ul><li>B2: drugs and toxins </li></ul><ul><ul><li>alcohols and glycols (methanol, propylene glycol) </li></ul></ul><ul><ul><ul><li>Overproduction of NADH in the liver </li></ul></ul></ul><ul><ul><li>Acetaminophen intoxication </li></ul></ul><ul><ul><ul><li>inhibiting mitochondrial respiration </li></ul></ul></ul><ul><ul><li>Cocaine intoxication </li></ul></ul><ul><ul><ul><li>seizures or other violent muscle activity , systemic hypoxia </li></ul></ul></ul>
  33. 33. 3.Etiology and Categories (4)type B3 <ul><li>B3: inborn errors of metabolism </li></ul><ul><ul><li>Glyconeogenesis enzyme deficiency </li></ul></ul><ul><ul><ul><li>glucose-6-phosphatase </li></ul></ul></ul><ul><ul><ul><li>fructose-1,6-diphosphatase </li></ul></ul></ul><ul><ul><ul><li>pyruvate carboxylase </li></ul></ul></ul><ul><ul><ul><li>pyruvate dehydrogenase </li></ul></ul></ul><ul><ul><li>MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) </li></ul></ul><ul><ul><ul><li>mutation in mitochondrial DNA gene </li></ul></ul></ul>
  34. 34. 4.Manifestation <ul><li>Hyperventilation ,dyspnea </li></ul><ul><li>Cardiovascular compromise is a frequent finding explaining many of the associated signs, which include cyanosis, cold extremities, tachycardia, hypotension, </li></ul><ul><li>lethargy, stupor or coma </li></ul><ul><li>pH , HC0 3 - ,AG , lactate </li></ul>
  35. 35. 5.Diagnosis <ul><li>History </li></ul><ul><li>Manifestation </li></ul><ul><li>Laboratory test </li></ul><ul><li>Exclude: </li></ul><ul><ul><li>DKA </li></ul></ul><ul><ul><li>Uremia </li></ul></ul><ul><ul><li>Intoxication: such as salicylates , by toxicology screen </li></ul></ul>
  36. 36. 5.Diagnosis- Laboratory test <ul><li>In critically ill patients, arterial lactate concentrations are essentially equivalent to those measured in blood sampled from central venous or from pulmonary artery catheter. </li></ul><ul><li>This is however not true for lactate measurements performed during cardiopulmonary resuscitation, where arterial concentrations are less than venous concentrations. </li></ul>
  37. 37. 5.Diagnosis- Laboratory test <ul><li>Serial determinations of lactate plasma concentration </li></ul><ul><ul><li>give useful information on the evolution of the metabolic processes </li></ul></ul><ul><ul><li>more powerful predictors of clinical outcome than a single determination of lactatemia. </li></ul></ul><ul><li>blood lactate must be measured as quickly as possible </li></ul><ul><ul><li>should be brought to the lab on ice </li></ul></ul>
  38. 38. 6.Treatment (1) type A <ul><li>improve tissue oxygenation is the only effective treatment </li></ul><ul><li>Maintenance of airway patency and oxygen delivery </li></ul><ul><ul><li>100% oxygen by mask </li></ul></ul><ul><ul><li>Intubate if the patient is unconscious, in severe shock, or otherwise in unstable condition. </li></ul></ul>
  39. 39. 6.Treatment (1) type A <ul><li>restoration of the circulating fluid volume </li></ul><ul><ul><li>Establish an intravenous line, Give a fluid bolus if the patient has tachycardia, hypotension or other signs of poor tissue perfusion </li></ul></ul><ul><li>improve cardiac function, such dobutamine </li></ul><ul><li>Monitor the cardiac rhythm </li></ul><ul><ul><li>Acidosis may predisposes to dysrhythmias </li></ul></ul><ul><li>Empirical antibiotic </li></ul>
  40. 40. 6. Treatment (2) Type B <ul><li>B1: identification of the primary illness and correction </li></ul><ul><ul><li>thiamine (50~100 mg IV followed by 50 mg/d orally for 1~2 wk) may be dramatic and potentially life saving </li></ul></ul><ul><ul><li>chemotherapy for malignant disorders </li></ul></ul><ul><li>B2: discontinuation of causative drugs </li></ul>
  41. 41. 6.Treatment (3) Alkalinization <ul><li>Controversial </li></ul><ul><ul><li>No Prospective studies have shown improved hemodynamics or outcomes </li></ul></ul><ul><ul><li>The hydrogen ion may be produced at 72 mmol/ min, alkaline therapy ’s value is doubtful (need 120ml/min 5%HCO 3 ) </li></ul></ul><ul><ul><li>Most studies show no change or decrease in intracellular pH </li></ul></ul><ul><ul><ul><li>Carbon dioxide leads to subsequent intracellular acidosis </li></ul></ul></ul>
  42. 42. 6.Treatment (3) Alkalinization <ul><li>Controversial </li></ul><ul><ul><li>may cause respiratory failure </li></ul></ul><ul><ul><li>Metabolic alkalosis </li></ul></ul><ul><ul><li>The administration of HCO 3 - has been observed to reduce cardiac performance in patients with cardiac arrest, CHF, and AMI. </li></ul></ul>
  43. 43. 6.Treatment (3) Alkalinization <ul><li>Conclusion </li></ul><ul><li>In cardiopulmonary resuscitation, sodium bicarbonate generally is not recommended </li></ul><ul><li>Toxic etiologies of lactic acidosis may use </li></ul><ul><li>intravenous NaHCO 3 - to keep the pH above 7.2 </li></ul>
  44. 44. 6.Treatment (4) Hemodialysis <ul><li>Dialysis or continuous hemofiltration </li></ul><ul><li>Consider hemodialysis in association with ethylene glycol and methanol poisoning. </li></ul><ul><li>useful mode of therapy when severe lactic acidosis exists in conjunction with renal failure or congestive heart failure. </li></ul>
  45. 45. 7. Prognosis <ul><li>the primary disorder is determinant </li></ul><ul><li>mortality rates may be 60%~80%,. </li></ul><ul><li>arterial lactate values of more than 5 mmlo/l on admission to ICU were associated with a mortality rate exceeding 80% at 30 days </li></ul><ul><li>lactate concentration >15 mmol/l, patients rarely survive </li></ul>
  46. 46. 8. D- Lactic Acidosi s <ul><li>Rare </li></ul><ul><li>D-Lactate made by bacteria from glucose and carbohydrate </li></ul><ul><ul><li>L-Lactate normally produced in human beings </li></ul></ul><ul><li>Lactate dehydrogenase can effectively metabolize only L-lactate, so if D-Lactate was absorbed, it will accumulate in blood </li></ul><ul><li>occur in patients with small bowel resections </li></ul><ul><li>Unexplained metabolic acidosis , AG increased </li></ul><ul><li>Treatment </li></ul><ul><ul><li>fluid resuscitation </li></ul></ul><ul><ul><li>restriction of simple sugars </li></ul></ul><ul><ul><li>NaHCO 3 administration as necessary </li></ul></ul>
  47. 47. Thank you