Download Lactic Acidosis

Lactic
Acidosis
Group Members
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Azam Muzafar Bin Ahmad Mokhtar (D20141066917)
Nur Hasyimah Binti Ruslan (D20141066899)
Nurhani Binti Nor Azwan (D20141066899)
Balqis Aqilah Binti Alue (D201410
Muhammad Noor Bin Khozari (D20141066906)
Huang Zheng Xian (D201410
PROBLEM STATEMENT
Lactic acidosis is a physiological condition characterized by low pH in body
tissues and blood (acidosis) accompanied by the buildup of lactate, especially Llactate, and is considered a distinct form of metabolic acidosis. Lactic acidosis is
characterized by lactate levels >5 mmol/L and serum pH <7.35. In a Young
Biochemist Association Forum, you are invited to explain about the condition
and how DCA could treat it.
What is Lactic Acidosis?
• Lactic acidosis is a physiological condition characterized by low pH
in body tissues and blood (acidosis) accompanied by the buildup of
lactate, especially L-lactate, and is considered a distinct form of
metabolic acidosis.
• The condition typically occurs when cells receive too little oxygen
(hypoxia), for example, during vigorous exercise. In this situation,
impaired cellular respiration leads to lower pH levels.
• Simultaneously, cells are forced to metabolize glucose anaerobically,
which leads to lactate formation. Therefore, elevated lactate is
indicative of tissue hypoxia, hypoperfusion, and possible damage.
Lactic Acidosis
• Occur when execessive accumulation of
lactic acid in bloodstream.
• Decrease activity pyruvate Dehydrogenase
CAUSES
• It can be divided by 2:
• 1. Can be prove clinically
 eg: left ventricular failure
• 2. Cannot be prove clinically
 Underlying diseases - eg: chronic kidney diseases,
diabetes, cancer
 Drug - alcohol, aspirin
 Inborn errors of metabolism - metabolism errors
Causes of Lactic Acidosis
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Genetic conditions
● Biotinidase deficiency, Multiple carboxylase deficiency, or non-genetic
deficiencies of biotin
● Diabetes mellitus and deafness
● Fructose 1,6-diphosphatase deficiency
● Glucose-6-phosphatase deficiency
● GRACILE syndrome
● Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
(MELAS)
● Pyruvate dehydrogenase deficiency
● Pyruvate carboxylase deficiency
How low oxygen level affect PDC?
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mitochondria oxidation in PDC of pyruvate
cannot proceed
Dichloroacetate Acid (DCA)
What is DCA?
• It’s molecular formula is CHCL2COOH
• DCA has been studied as potential drugs
• Inhibits pyruvate dehydrogenase kinase that is responsible in
inactivate the mitochondrial pyruvate dehydrogenase.
How the activity of PDC affected by Dichloroacetate?
• DCA ( an inhibitor of pyruvate dehydrogenase kinase) is
a useful tool on regulation of PDC.
• DCA indirectly activate the PDC by inhibit PD kinase as
pyruvate
• DCA stimulates the metabolic process (pyruvate
oxidation)
• DCA only effective when blood glucose maintained by
gluconeogenesis.
How DCA works?
Glycolysis ends with the synthesis of
pyruvate.
But to be self-functioning it must end with
lactate. ( low oxygen)
Which mean accumalation of pyruvate lead to
excess lactate production.
DCA active pyruvate dehydrogenase (PDH)
which will stimulate the oxidation of lactate to
acetyl-coenzyme A and carbon dioxide.
Extra Info
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This New Drug(DCA) Appears to Cause Cancer Cells to Self-Destruct, however, whether it can reverse
tumor growth without harming you in other ways remains to be seen.
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In a test of using DCA in the treatment of lactic acidosis patient, it is observed that dichloroacetate decreased
the lactate concentrations in the treated patients but had no beneficial effects on outcomes. The authors
concluded that dichloroacetate treatment of patients with severe lactic acidosis results in statistically
significant but clinically unimportant changes in arterial blood lactate concentrations and pH and fails to alter
either hemodynamics or survival rates.