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acidosis
explain about the condition
and how DCA could treat it.
Symptoms
Shallow breathing
Decreased appetite
Abdominal pain
The activity of the pyruvate dehydrogenase complex decrease due to the low concentration of
oxygen.
If the oxygen available is insufficient(hypoxia) ,thus the pyruvate will convert into lactate catalyse
by the lactate dehydrogenase in an anaerobic respiration instead of the acetyl-CoA.
PDC kinase cause the inactivation of PDC,inhibiting pyruvate oxidation. Persistent glycolysis
without pyruvate oxidation leads to accumulation of lactate.
Mutations of subunits of the PDC system cause damage of the activity of the enzyme complex
are likely to lead to lactate accumulation
The consequent rise in the intramitochondrial NADH/NAD ratio inhibits PDC activity that
cause pyruvate oxidation decreases, and pyruvate is converted to lactate, resulting in an
increased lactate
DCA -dichloroacetate
PDK - pyruvate dehydrogenase kinase
PDC- pyruvate dehyrogenase complex
PDH- pyruvate dehydrogenase
Pyruvate dehydrogenase is the enzyme that will catalyse the oxidative decarboxylation of
pyruvate to acetyl CoA
PDH complex can be existed in two forms: Phosphorylated & dephosphorylated
when PDC is in its active form, pyruvate can be converted to Acetyl CoA
NADH, ATP,
ACETYLCOA IS
REGULATO
R FOR
SYSTEM
DCA WILL
INHIBIT
PDH
KINASE
INCREASE
PDH
ACTIVITY
# When the circulation is restored, the liver can metabolise the circulating
lactate. If lactic acidosis is severe and the cause cannot be corrected, the
mortality can be quite high.
CONCLUSION
Lactic Acidosis : occurs in association with a wide variety of underlying processes
and may represent a well-tolerated, physiologic event or a life-threatening,
pathologic condition. Overall, theres 2 type of LA : A & B
Lactic acidosis is classified based upon oxygen supply to the tissues. Type A is
that clearly associated with clinically evident hypoperfusion or hypoxia, and type B
includes all other forms, those in which there is no evidence of tissue anoxia.
Lactic acidosis is often diagnosed during the evaluation of an anion gap
acidosis. Treatment is directed toward identification and correction of the
underlying disorder and restitution of normal acid-base equilibrium. (This is the
basic therapeutic goals in treatment of LA)
CONCLUSION
Dichloroacetate (DCA) is an experimental drug that increases the activity of
pyruvate dehydrogenase, and this promotes the oxidation of glucose,
pyruvate, and lactate and thus reduces blood lactate levels. Since oxygen is
required for this metabolic process, DCA has no role in treatment of type A
lactic acidosis. Its role in therapy for type B lactic acidosis may be limited by
the increased ketosis and neurologic complications that occur with its use.
The fact that so many experimental therapies have been tried in lactic
acidosis reflects the poor outcome of this disorder with the use of
current treatment. The mortality of patients with type A lactic acidosis is
approximately 80 percent; with type B it is 50 to 80 percent. Earlier
recognition and correction of the underlying disorder responsible for the
lactic acidosis is the best hope for reduction of this high mortality