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Lactic acidosis , diagnosis, causes, management
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- 2. INTRODUCTION Lactic acidis the normal endpoint of the anaerobic breakdown of glucose in the tissues Normal plasma lactate: 0.5 to 1.5 meq/L
- 3. DEFINITION Lactic acidosisis a pathological state diagnosed when the serum concentration of lactate or lactic acid is persistently 5mmol/l or greater There is significant acidemia and serum pH< 7.35
- 4. FORMATION OF LACTICACID RBCs, brain and skin are major sources of lactic acid During exercise skeletal muscles release significant amount of lactic acid Liver and kidneys utilize lactic acid for biosynthesis of glucose It is catalyzed by the enzyme lactate dehydrogenase
- 5. The bodytissues produces 1500 mmoles of lactate each day The lactate enters blood stream and metabolized meanly by liver (60% in Cori Cycle) and kidneys (30%) to glucose All tissues can produce lactate under anaerobic conditions Skeletal muscles produce high amounts of lactate during vigorous exercise Oxygen may not reach the muscle fast enough to keep up with the workout LACTATE METABOLISM IN TISSUE
- 8. PYRUVATE TO LACTATE The reduction of pyruvate by NADH+ catalyzed by to form lactate by lactate dehydrogenase on anaerobic glycolysis to generate ATP The reaction takes place in the cells when the amount of oxygen is less, as in muscle during intense activity Pyruvate lactate regenerates NAD+ which prevents glycolysis from cease to function Lactate cannot be used to generate energy Lactate must be removed from the muscles to prevent lactic acidosis
- 9. Carried by the Bloodto the Liver to be converted into Glucose
- 10. CORI CYCLE Itis named after Carl Cori and Gerty Cori in 1929 It is also known as lactic acid cycle or glucose lactate or lactic acid fermentation It involves the synthesis of glucose through gluconeogenesis from lactate synthesized in the skeletal muscle It occurs when the muscles need energy or during hypoxia -Intense exercise -Sprinting
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- 13. Table No.1 Lactate-Producingand -Consuming Tissues Under Basal Condition Producers Consumers Skin Liver Erythrocytes Renal Cortex Brain Skeletal Muscles Platelets Leukocytes Renal Medulla Tissues of the Eye (Cornea, Lens, Retina)
- 14. WHERE IS LACTICACID FOUND ?
- 16. PATHOPHYSIOLOGY OF LACTICACIDOSIS Lactic acidosis occurs whenever there is Increased lactic acid production and decreased utilization Types and causes of Lactic acidosis 1. Types A (hypoxic) 2. Types B (metabolic)
- 17. Type A Due to hypoxia in tissues (most common) Hypoxia causes impaired oxidative phosphorylation and decreased ATP synthesis To survive ,the cells switch to anaerobic glycolysis for ATP synthesis This produces lactate as a final product The amount of oxygen required to recover oxygen deficiency (Hypoxia) is called oxygen debt
- 18. Type Ais due to inadequate oxygen delivery in tissues Myocardial infarction Pulmonary embolism Tissue hypoperfusion( shock, cardiac arrest) Increased tissue demand (exercise, seizures, sepsis)
- 19. Type B Due to disorders in carbohydrate metabolism ― Congenital lactic acidosis is due to deficiency of pyruvate dehydrogenase enzyme Chronic hepatic disease a company by shock or bleeding Drug intoxication(ethanol, salicylate) Combination Malignancy, Diabetes, Alcohol , HIV and Thiamine deficiency
- 20. General malaise Loss of weight and loss of appetite Weakness and fatigue Nausea, and vomiting Tachypnoea Tachycardia SIGNS AND SYMPTOMS
- 21. DIAGNOSIS Diagnosis done bymeasuring blood lactate levels Hyperlactemia: 2-5 mmols/L Severe lactic acidosis: >5mmols/L
- 22. TREATMENT Treatment underlyingdisease Sodium bicarbonate hemodialysis
- 23. SODIUM BICARBONATE Sodiumbicarbonate: May worsen oxygen delivery ,increase lactate production especially in hypoxia induced glycolysis The surviving sepsis campaign recommended hold sodium bicarbonate unless profound lactic acidosis and academia ( arterial pH less than 7.1 and serum bicarbonate 6meq/L or less)
- 24. ALTERNATIVES TO BICARBONATE THERAPY Tromethamine (tris-hydroxymethyl aminomethane also called THAM, TRIS and TROMETAMOL Carbicarb Dichloroacetate (DCA) None of these alternative agents have shown benefit in pts with lactic acidosis
- 25. TRIS HYDROXYMETHYL AMINOMETHANE (THAM) It is weak alkali and has a benefit over bicarbonate as it produce less CO2 Clinical trails do not prove THAM to be more effective than bicarbonate
- 26. CARBICARB It isan equimolar combination of sodium carbonate and sodium bicarbonate that produce less CO2 than sodium bicarbonate alone Trials have not proven any reduction in mortality and morbidity
- 27. DICHLOROACETATE It isan activator of pyruvate dehydrogenase It can lower conc: of lactic acid in pts by improving the lactate utilization When used in large clinical trail it did not have any effect on mortality DCA helpful in lactic acidosis in children with severe malaria
- 28. HAEMODIALYSIS It israrely indicated as a treatment for lactic acidosis It is used in drug toxicity ( Metformin induced lactic acidosis)to speed up elimination of drug/toxin It is helpful when fluid overload and cardiac or renal insufficiency is present
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