logging in or signing up LACTIC ACIDOSIS dranishjoshi Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1140 Category: Entertainment License: All Rights Reserved Like it (0) Dislike it (1) Added: December 18, 2009 This Presentation is Public Favorites: 2 Presentation Description No description available. Comments Posting comment... By: afifyicu (14 month(s) ago) VERY TO THE POINT PRESENTATION SMOOTH AND PRECISE Saving..... Post Reply Close Saving..... Edit Comment Close By: Peekay001 (20 month(s) ago) This is a must read for all practising physicians! Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript METABOLIC ACIDOSIS: : METABOLIC ACIDOSIS: Metabolic acidosis is state of decreased systemic pH resulting from either a primary increase in (H+) or a reduction in (HCO3-) concentrations. pH<7.35 In acute state, respiratory compensation of acidosis occurs by hyperventilation resulting in a relative reduction in PaCO2. Chronically, renal compensation occurs by means of reabsorption of HCO3. ANION GAP=Na-(Hco3+cl)=+/-12 : ANION GAP=Na-(Hco3+cl)=+/-12 WIDE ANION GAP NORMAL ANION GAP (HCL) -Lactic acid -Renal HCO3 loss -Ketoacids -GI HCO3 loss -Renal failure. -HCl consumption: -Ingestions : TPN Methanol Ethylene glycol Salicylates INTRODUCTION: : INTRODUCTION: Lactic acidosis, identified by a state of acidosis and an elevated plasma lactate concentration is one type of anion gap metabolic acidosis and may result from numerous conditions. Normal blood lactate concentration: unstressed patients =0.5-1 mmol/L. critical illness <2 mmol/L. Hyperlactatemia: mild-to-moderate persistent increase in blood lactate concentration (2-5 mmol/L) without metabolic acidosis. Lactic acidosis: persistently increased blood lactate levels (usually >4-5 mmol/L) in association with metabolic acidosis PH <7.35. Pathophysiology: : Pathophysiology: Predominate source of carbon atoms for glucose synthesis by gluconeogenesis. In anaerobic glycolysis(RBC’s, muscle), Pyruvate Lactate LDH NADH NAD+ Glycolysis LDH reaction involves NADH NAD+ is then available for use in the glyceraldehydes reaction in glycolysis. Cori (KREBS) cycle : Cori (KREBS) cycle Lactate is released into blood to liver to be converted to glucose. NADH is increased. Intracellular redox potential shifts from aerobic to anaerobic metabolism. Decrease in pyruvate carboxylase activity (rate limiting enzyme in the formation of glucose from lactate) results in decreased hepatic metabolism of lactate. 1400 mmol lactate produced daily. Buffered by 1400 mmol of HCO3 to form Na-lactate. Liver responsible for oxidizing lactate to restore HCO3 consumed. this must work well, because normal plasma concentrations of lactate are < 1mmol. Kidney, Extrahepatic tissues also contribute to lactate removal (10-20%). Kidneys help via excretion, gluconeogenesis, and oxidation. LACTATE: : LACTATE: Lactic acid exists in 2 forms, the L-lactate and D-lactate. L-lactate is the most commonly measured level, as it is the only form produced in human metabolism. Its excess represents increased anaerobic metabolism due to tissue hypoperfusion. D-lactate is a byproduct of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small-bowel resection. Hyperlactatemia:Spectrum of Syndromes : Hyperlactatemia:Spectrum of Syndromes Compensated or Decompensated or asymptomatic symptomatic lactic acidosis/hepatic steatosis – Chronic – Rapidly progressive – Stable over time – Life-threatening – HCO3 ≥ 20 mmol/L – HCO3 <20 mmol/L – Common – Rare Roubenoff R, et al. AIDS. 1999;13:1373-1375. Cohen-Woods Classification : Cohen-Woods Classification Cohen R, Woods H. Clinical and Biochemical Aspects of Lactic Acidosis. Blackwell Scientific Publications; 1976. Causes: : Causes: (type A): Overproduction: Circulatory insufficiency (shock, cardiac failure), -Pulmonary disorders, -Hemoglobin transfer disorders (severe anemia) Underutilization: Liver disease, -Gluconeogenesis inhibition, -Thiamine deficiency, -Uncoupled oxidative phosphorylation, -Mitochondrial enzyme defects, and inhibitors (carbon monoxide, cyanide) Causes: : Causes: (type B): Type B1: systemic disease such as -renal and hepatic failure, -diabetes, and malignancy. -severe infections (cholera, malaria), -seizures. Type B2: drugs and toxins including -Alcohols: ethanol, methanol, propylene glycol, -Biguanides: phenformin, metformin -Beta-adrenergic agents: epinephrine, ritodrine, terbutaline -Cyanogenic compounds: cyanide,nitriles, nitroprusside Causes: : Causes: -HIV drugs: zidovudine, didanosine, lamivudine -Iron, isoniazid, -salicylates (acetaminophen). -sulfasalazine, and valproic acid. -Halothane,propofol. Type B3: inborn errors of metabolism -G-6-phosphatase deficiency (von Gierke disease), -fructose-1,6-diphosphatase deficiency, -pyruvate carboxylase deficiency, -pyruvate dehydrogenase deficiency, -oxidative phosphorylation deficiency, -methylmalonic aciduria. Bret A Nicks, MD, Assistant Professor, Assistant Medical Director, Department of Emergency Medicine, Wake Forest University Health Sciences;Apr 9, 2008 D-Lactic Acidosis : D-Lactic Acidosis This unique form of lactic acidosis can occur in patients with - jejunoileal bypasses, - small bowel resections, - short-bowel syndrome. Bacteria are responsible for metabolizing glucose and carbohydrate to D-lactic acid, which is then systemically absorbed. Lactate dehydrogenase can effectively metabolize only L-lactate; D-lactate is only slowly metabolized by human subjects. The anion gap is commonly smaller than expected on the basis of the HCO3 decrease, because D-lactate is not very well absorbed by renal tubules. The increased anion gap may be the result of D-lactate or some as yet unknown absorbed toxin. D-Lactic Acidosis : D-Lactic Acidosis Treatment: - fluid resuscitation, - restriction of simple sugars, - NaHCO3 administration as necessary, - judicious use of antibiotics (such as metronidazole). because antibiotics can precipitate the syndrome by permitting overgrowth of lactobacilli. Uribarri J, Oh MS, Carroll HJ: D-Lactic acidosis. Medicine 77:73 -82, 1998] Clinical : Clinical History: No single historical feature indicative of the presence of lactic acidosis, as symptoms are dependent on the underlying etiology. a careful history is vital to determine the underlying pathology. Historical features such as recent or chronic illnesses, change in medications (e.g., biguanides, antiretrovirals), or potential toxicologic interactions should be solicited. Physical findings: depends on the underlying cause of lactic acidosis. Signs of cardiovascular compromise: cyanosis , cool extremities, tachycardia, hypotension, dry mucous membranes, dyspnea, confusion, lethargy, stupor, or coma. Hyperventilation: compensatory mechanism causing respiratory alkalosis. Systemic effects of acidosis : Systemic effects of acidosis Respiratory Dyspnea, tachypnea, Kussmaul respirations Increased minute ventilation Decreased diaphragm contractility Cardiac Decreased catecholamine responsiveness Decreased fibrillation threshold Decreased contractility at pH <7.1 Increased heart rate and contractility at pH >7.2 Neurological Increased cerebral blood flow Decreased cerebral metabolism Altered mental status Increase sympathetic catecholamine discharge Other Decreased renal and hepatic perfusion Increased metabolic rate Increased protein catabolism Laboratory studies : Laboratory studies Anion gap (AG)= sodium - [HCO3 + chloride]). (ABG) analysis: Base deficit, Acidemia is required for the diagnosis. Serum lactate level New devices :near-infrared spectroscopy, correlation between tissue perfusion and lactate levels Treatment: : Treatment: Emergency department care: -Identification of the primary illness and directed therapy. -Restoration of tissue oxygen delivery. - Early Goal-directed therapy for sepsis. -Appropriate measures include treatment of shock, -restoration of circulating fluid volume, -improved cardiac function, -identification of sepsis source and appropriate therapy -resection of any potential ischemic regions. correction of the underlying disorder: include the -administration of appropriate antibiotics, -surgical drainage or debridement, -chemotherapy for malignancy, -discontinuation of potentially causative medications, -dietary modification in inborn errors of metabolism. Medications: : Medications: Sodium bicarbonate: The starting dose is one third to one half of the calculated extracellular bicarbonate deficit: HCO3 deficit (in meq) = 0.5 X (Wt in kg) X (Desired HCO3 - Measured HCO3) Metabolic alkalosis & increase in PvCO2 can ensue after bicarbonate administration. Tris - [hydroxymethyl] aminomethane: theoretical advantages over bicarbonate because CO2 is not generated. Medications: : Medications: Carbicarb: combination of sodium carbonate and sodium bicarbonate that buffers comparably to bicarbonate but does not generate CO2. Dichloroacetate: not a buffer, but it stimulates the oxidation of pyruvate. This has resulted in improved lactate utilization and increased tissue levels of ATP. Prospective studies have failed to demonstrate its efficacy. Thiamine: The response to thiamine repletion (given as 50-100 mg IV followed by 50 mg/d PO for 1-2 wk) may be dramatic and potentially life saving. Miscellaneous agents: Coenzyme Q, l-carnitine, and riboflavin have been used to treat lactic acidosis due to antiretroviral therapy, without definitive demonstration of efficacy. Mortality/morbidity : Mortality/morbidity disorder of lactate metabolism are typically significantly ill and are at risk for developing multiple organ failure. mortality rate that increases nearly linearly with the concentration of serum lactate. Several studies have shown that vigilant correction of hyperlactemia is associated with decreased morbidity and mortality. The mortality rate of patients with a serum lactate level greater than 2 mmol/L persisting after 24 hours with an associated acidemia approaches 70%. Prognosis: : Prognosis: Serum lactate levels above 4mmol/L were associated with a survival of only 11% in critically ill ICU patients if persistent after 24 hours. Further studies have demonstrated an association between a 12-hour rise in lactate concentration above 2.5 mmol/L and multisystem organ failure. The duration and degree of increased serum lactic acid appear to predict morbidity and mortality. Abramson et al identified 100% survival with normalization of serum lactate concentration (<2mmol/L) within the first 24 hours following multiple trauma, 78% survival if normalization occurred in 24-48 hours, only 14% survival if after 48 hours.2 Clinical Trials for Lactic Acidosis : Clinical Trials for Lactic Acidosis Study of the Metabolism of Pyruvate and Related Problems in Patients With Lactic Acidemia - This study is currently recruiting patients (Current: 23 Nov 2006) Phase III Randomized Study of Sodium Dichloroacetate in Children With Congenital Lactic Acidosis - This study is no longer recruiting patients (Current: 23 Nov 2006) - sodium dichloroacetate Phase II Pilot Randomized Study of Sodium Dichloroacetate in Patients With Congenital Lactic Acidemia - This study is currently recruiting patients (Current: 23 Nov 2006) - sodium dichloroacetate Lactate Metabolism Study in HIV Infected Persons - This study is currently recruiting patients (Current: 23 Nov 2006) Prevention of Dichloroacetate Toxicity - This study is currently recruiting patients (Current: 23 Nov 2006) - Nitisinone (NTBC),Dichloroacetate You do not have the permission to view this presentation. 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LACTIC ACIDOSIS dranishjoshi Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1140 Category: Entertainment License: All Rights Reserved Like it (0) Dislike it (1) Added: December 18, 2009 This Presentation is Public Favorites: 2 Presentation Description No description available. Comments Posting comment... By: afifyicu (14 month(s) ago) VERY TO THE POINT PRESENTATION SMOOTH AND PRECISE Saving..... Post Reply Close Saving..... Edit Comment Close By: Peekay001 (20 month(s) ago) This is a must read for all practising physicians! Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript METABOLIC ACIDOSIS: : METABOLIC ACIDOSIS: Metabolic acidosis is state of decreased systemic pH resulting from either a primary increase in (H+) or a reduction in (HCO3-) concentrations. pH<7.35 In acute state, respiratory compensation of acidosis occurs by hyperventilation resulting in a relative reduction in PaCO2. Chronically, renal compensation occurs by means of reabsorption of HCO3. ANION GAP=Na-(Hco3+cl)=+/-12 : ANION GAP=Na-(Hco3+cl)=+/-12 WIDE ANION GAP NORMAL ANION GAP (HCL) -Lactic acid -Renal HCO3 loss -Ketoacids -GI HCO3 loss -Renal failure. -HCl consumption: -Ingestions : TPN Methanol Ethylene glycol Salicylates INTRODUCTION: : INTRODUCTION: Lactic acidosis, identified by a state of acidosis and an elevated plasma lactate concentration is one type of anion gap metabolic acidosis and may result from numerous conditions. Normal blood lactate concentration: unstressed patients =0.5-1 mmol/L. critical illness <2 mmol/L. Hyperlactatemia: mild-to-moderate persistent increase in blood lactate concentration (2-5 mmol/L) without metabolic acidosis. Lactic acidosis: persistently increased blood lactate levels (usually >4-5 mmol/L) in association with metabolic acidosis PH <7.35. Pathophysiology: : Pathophysiology: Predominate source of carbon atoms for glucose synthesis by gluconeogenesis. In anaerobic glycolysis(RBC’s, muscle), Pyruvate Lactate LDH NADH NAD+ Glycolysis LDH reaction involves NADH NAD+ is then available for use in the glyceraldehydes reaction in glycolysis. Cori (KREBS) cycle : Cori (KREBS) cycle Lactate is released into blood to liver to be converted to glucose. NADH is increased. Intracellular redox potential shifts from aerobic to anaerobic metabolism. Decrease in pyruvate carboxylase activity (rate limiting enzyme in the formation of glucose from lactate) results in decreased hepatic metabolism of lactate. 1400 mmol lactate produced daily. Buffered by 1400 mmol of HCO3 to form Na-lactate. Liver responsible for oxidizing lactate to restore HCO3 consumed. this must work well, because normal plasma concentrations of lactate are < 1mmol. Kidney, Extrahepatic tissues also contribute to lactate removal (10-20%). Kidneys help via excretion, gluconeogenesis, and oxidation. LACTATE: : LACTATE: Lactic acid exists in 2 forms, the L-lactate and D-lactate. L-lactate is the most commonly measured level, as it is the only form produced in human metabolism. Its excess represents increased anaerobic metabolism due to tissue hypoperfusion. D-lactate is a byproduct of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small-bowel resection. Hyperlactatemia:Spectrum of Syndromes : Hyperlactatemia:Spectrum of Syndromes Compensated or Decompensated or asymptomatic symptomatic lactic acidosis/hepatic steatosis – Chronic – Rapidly progressive – Stable over time – Life-threatening – HCO3 ≥ 20 mmol/L – HCO3 <20 mmol/L – Common – Rare Roubenoff R, et al. AIDS. 1999;13:1373-1375. Cohen-Woods Classification : Cohen-Woods Classification Cohen R, Woods H. Clinical and Biochemical Aspects of Lactic Acidosis. Blackwell Scientific Publications; 1976. Causes: : Causes: (type A): Overproduction: Circulatory insufficiency (shock, cardiac failure), -Pulmonary disorders, -Hemoglobin transfer disorders (severe anemia) Underutilization: Liver disease, -Gluconeogenesis inhibition, -Thiamine deficiency, -Uncoupled oxidative phosphorylation, -Mitochondrial enzyme defects, and inhibitors (carbon monoxide, cyanide) Causes: : Causes: (type B): Type B1: systemic disease such as -renal and hepatic failure, -diabetes, and malignancy. -severe infections (cholera, malaria), -seizures. Type B2: drugs and toxins including -Alcohols: ethanol, methanol, propylene glycol, -Biguanides: phenformin, metformin -Beta-adrenergic agents: epinephrine, ritodrine, terbutaline -Cyanogenic compounds: cyanide,nitriles, nitroprusside Causes: : Causes: -HIV drugs: zidovudine, didanosine, lamivudine -Iron, isoniazid, -salicylates (acetaminophen). -sulfasalazine, and valproic acid. -Halothane,propofol. Type B3: inborn errors of metabolism -G-6-phosphatase deficiency (von Gierke disease), -fructose-1,6-diphosphatase deficiency, -pyruvate carboxylase deficiency, -pyruvate dehydrogenase deficiency, -oxidative phosphorylation deficiency, -methylmalonic aciduria. Bret A Nicks, MD, Assistant Professor, Assistant Medical Director, Department of Emergency Medicine, Wake Forest University Health Sciences;Apr 9, 2008 D-Lactic Acidosis : D-Lactic Acidosis This unique form of lactic acidosis can occur in patients with - jejunoileal bypasses, - small bowel resections, - short-bowel syndrome. Bacteria are responsible for metabolizing glucose and carbohydrate to D-lactic acid, which is then systemically absorbed. Lactate dehydrogenase can effectively metabolize only L-lactate; D-lactate is only slowly metabolized by human subjects. The anion gap is commonly smaller than expected on the basis of the HCO3 decrease, because D-lactate is not very well absorbed by renal tubules. The increased anion gap may be the result of D-lactate or some as yet unknown absorbed toxin. D-Lactic Acidosis : D-Lactic Acidosis Treatment: - fluid resuscitation, - restriction of simple sugars, - NaHCO3 administration as necessary, - judicious use of antibiotics (such as metronidazole). because antibiotics can precipitate the syndrome by permitting overgrowth of lactobacilli. Uribarri J, Oh MS, Carroll HJ: D-Lactic acidosis. Medicine 77:73 -82, 1998] Clinical : Clinical History: No single historical feature indicative of the presence of lactic acidosis, as symptoms are dependent on the underlying etiology. a careful history is vital to determine the underlying pathology. Historical features such as recent or chronic illnesses, change in medications (e.g., biguanides, antiretrovirals), or potential toxicologic interactions should be solicited. Physical findings: depends on the underlying cause of lactic acidosis. Signs of cardiovascular compromise: cyanosis , cool extremities, tachycardia, hypotension, dry mucous membranes, dyspnea, confusion, lethargy, stupor, or coma. Hyperventilation: compensatory mechanism causing respiratory alkalosis. Systemic effects of acidosis : Systemic effects of acidosis Respiratory Dyspnea, tachypnea, Kussmaul respirations Increased minute ventilation Decreased diaphragm contractility Cardiac Decreased catecholamine responsiveness Decreased fibrillation threshold Decreased contractility at pH <7.1 Increased heart rate and contractility at pH >7.2 Neurological Increased cerebral blood flow Decreased cerebral metabolism Altered mental status Increase sympathetic catecholamine discharge Other Decreased renal and hepatic perfusion Increased metabolic rate Increased protein catabolism Laboratory studies : Laboratory studies Anion gap (AG)= sodium - [HCO3 + chloride]). (ABG) analysis: Base deficit, Acidemia is required for the diagnosis. Serum lactate level New devices :near-infrared spectroscopy, correlation between tissue perfusion and lactate levels Treatment: : Treatment: Emergency department care: -Identification of the primary illness and directed therapy. -Restoration of tissue oxygen delivery. - Early Goal-directed therapy for sepsis. -Appropriate measures include treatment of shock, -restoration of circulating fluid volume, -improved cardiac function, -identification of sepsis source and appropriate therapy -resection of any potential ischemic regions. correction of the underlying disorder: include the -administration of appropriate antibiotics, -surgical drainage or debridement, -chemotherapy for malignancy, -discontinuation of potentially causative medications, -dietary modification in inborn errors of metabolism. Medications: : Medications: Sodium bicarbonate: The starting dose is one third to one half of the calculated extracellular bicarbonate deficit: HCO3 deficit (in meq) = 0.5 X (Wt in kg) X (Desired HCO3 - Measured HCO3) Metabolic alkalosis & increase in PvCO2 can ensue after bicarbonate administration. Tris - [hydroxymethyl] aminomethane: theoretical advantages over bicarbonate because CO2 is not generated. Medications: : Medications: Carbicarb: combination of sodium carbonate and sodium bicarbonate that buffers comparably to bicarbonate but does not generate CO2. Dichloroacetate: not a buffer, but it stimulates the oxidation of pyruvate. This has resulted in improved lactate utilization and increased tissue levels of ATP. Prospective studies have failed to demonstrate its efficacy. Thiamine: The response to thiamine repletion (given as 50-100 mg IV followed by 50 mg/d PO for 1-2 wk) may be dramatic and potentially life saving. Miscellaneous agents: Coenzyme Q, l-carnitine, and riboflavin have been used to treat lactic acidosis due to antiretroviral therapy, without definitive demonstration of efficacy. Mortality/morbidity : Mortality/morbidity disorder of lactate metabolism are typically significantly ill and are at risk for developing multiple organ failure. mortality rate that increases nearly linearly with the concentration of serum lactate. Several studies have shown that vigilant correction of hyperlactemia is associated with decreased morbidity and mortality. The mortality rate of patients with a serum lactate level greater than 2 mmol/L persisting after 24 hours with an associated acidemia approaches 70%. Prognosis: : Prognosis: Serum lactate levels above 4mmol/L were associated with a survival of only 11% in critically ill ICU patients if persistent after 24 hours. Further studies have demonstrated an association between a 12-hour rise in lactate concentration above 2.5 mmol/L and multisystem organ failure. The duration and degree of increased serum lactic acid appear to predict morbidity and mortality. Abramson et al identified 100% survival with normalization of serum lactate concentration (<2mmol/L) within the first 24 hours following multiple trauma, 78% survival if normalization occurred in 24-48 hours, only 14% survival if after 48 hours.2 Clinical Trials for Lactic Acidosis : Clinical Trials for Lactic Acidosis Study of the Metabolism of Pyruvate and Related Problems in Patients With Lactic Acidemia - This study is currently recruiting patients (Current: 23 Nov 2006) Phase III Randomized Study of Sodium Dichloroacetate in Children With Congenital Lactic Acidosis - This study is no longer recruiting patients (Current: 23 Nov 2006) - sodium dichloroacetate Phase II Pilot Randomized Study of Sodium Dichloroacetate in Patients With Congenital Lactic Acidemia - This study is currently recruiting patients (Current: 23 Nov 2006) - sodium dichloroacetate Lactate Metabolism Study in HIV Infected Persons - This study is currently recruiting patients (Current: 23 Nov 2006) Prevention of Dichloroacetate Toxicity - This study is currently recruiting patients (Current: 23 Nov 2006) - Nitisinone (NTBC),Dichloroacetate